Rong Xiao - Academia.edu (original) (raw)

Papers by Rong Xiao

Research paper thumbnail of Crystal structure of bacterial citrate lyase

Acta Crystallographica Section A Foundations of Crystallography

Yb 3+ -co-doped YAG transparent ceramic nano-powders were prepared by carbonate altogether precip... more Yb 3+ -co-doped YAG transparent ceramic nano-powders were prepared by carbonate altogether precipitation methods, and theirstructure, morphology and properties were also analyzed by X-ray diffraction, absorption and fluorescence spectra. The results show Yb3+:YAG nano-powders are obtained with higher sintering performance and purity, and the particle shapes are regular with average diameter in the range of 100 nm. The crystalline size grew with the increase of the heat treatment temperature. The size of powder calcined at 1100ºC was about 70-150 nm, which is favorable for good sinterability of Yb3+: YAG ceramics.

Research paper thumbnail of Northeast Structural Genomics Consortium

We report NMR assignments and solution structure of the 71-residue 30S ribosomal protein S28E fro... more We report NMR assignments and solution structure of the 71-residue 30S ribosomal protein S28E from the archaean Pyrococcus horikoshii, target JR19 of the Northeast Structural Genomics Consortium. The structure, determined rapidly with the aid of automated backbone resonance assignment (AutoAssign) and automated structure determination (AutoStructure) software, is characterized by a four-stranded �-sheet with a classic Greek-key topology and an oligonucleotide/oligosaccharide �-barrel (OB) fold. The electrostatic surface of S28E exhibits positive and negative patches on opposite sides, the former constituting a putative binding site for RNA. The 13 C-terminal residues of the protein contain a consensus sequence motif constituting the signature of the S28E protein family. Surprisingly, this C-terminal segment is unstructured in solution. Keywords: Ribosomal protein; Greek-key motif; NMR structure; Northeast Structural Genomics Consortium The field of structural genomics aims at elucid...

Research paper thumbnail of A Community Resource of Experimental Data for NMR - X-ray Crystal Structure Pairs

Protein science : a publication of the Protein Society, Jan 21, 2015

We have developed an on-line NMR/X-ray Structure Pair Data Repository. The NIGMS Protein Structur... more We have developed an on-line NMR/X-ray Structure Pair Data Repository. The NIGMS Protein Structure Initiative (PSI) has provided many valuable reagents, 3D structures, and technologies for structural biology. The Northeast Structural Genomics Consortium was one of several PSI centers. NESG used both X-ray crystallography and NMR spectroscopy for protein structure determination. A key goal of the PSI was to provide experimental structures for at least one representative of each of hundreds of targeted protein domain families. In some cases, structures for identical (or nearly identical) constructs were determined by both NMR and X-ray crystallography. NMR spectroscopy and X-ray diffraction data for 41 of these "NMR/X-ray" structure pairs determined using conventional triple-resonance NMR methods with extensive sidechain resonance assignments have been organized in an on-line NMR/X-ray Structure Pair Data Repository. In addition, several NMR data sets for perdeuterated, meth...

Research paper thumbnail of The RAS-Binding Domain of Human BRAF Protein Serine/Threonine Kinase Exhibits Allosteric Conformational Changes upon Binding HRAS

Research paper thumbnail of The NMR solution structure of the 30S ribosomal protein S27e encoded in gene RS27_ARCFU of Archaeoglobus fulgidis reveals a novel protein fold

Protein Science, 2004

The Archaeoglobus fulgidis gene RS27_ARCFU encodes the 30S ribosomal protein S27e. Here, we prese... more The Archaeoglobus fulgidis gene RS27_ARCFU encodes the 30S ribosomal protein S27e. Here, we present the high-quality NMR solution structure of this archaeal protein, which comprises a C4 zinc finger motif of the CX 2 CX 14-16 CX 2 C class. S27e was selected as a target of the Northeast Structural Genomics Consortium (target ID: GR2), and its three-dimensional structure is the first representative of a family of more than 116 homologous proteins occurring in eukaryotic and archaeal cells. As a salient feature of its molecular architecture, S27e exhibits a ␤-sandwich consisting of two three-stranded sheets with topology B(↓), A(↑), F(↓), and C(↑), D(↓), E(↑). Due to the uniqueness of the arrangement of the strands, the resulting fold was found to be novel. Residues that are highly conserved among the S27 proteins allowed identification of a structural motif of putative functional importance; a conserved hydrophobic patch may well play a pivotal role for functioning of S27 proteins, be it in archaeal or eukaryotic cells. The structure of human S27, which possesses a 26-residue amino-terminal extension when compared with the archaeal S27e, was modeled on the basis of two structural templates, S27e for the carboxy-terminal core and the amino-terminal segment of the archaeal ribosomal protein L37Ae for the extension. Remarkably, the electrostatic surface properties of archaeal and human proteins are predicted to be entirely different, pointing at either functional variations among archaeal and eukaryotic S27 proteins, or, assuming that the function remained invariant, to a concerted evolutionary change of the surface potential of proteins interacting with S27.

Research paper thumbnail of GFT NMR based resonance assignment for the 21 kDa human protein UFC1

Journal of Biomolecular Nmr, 2005

Protein UFC1 (NCBI ID: 9606) is target of the Northeast Structural Genomics Consortium (ID HR41) ... more Protein UFC1 (NCBI ID: 9606) is target of the Northeast Structural Genomics Consortium (ID HR41) and belongs to a family of at least 22 homologues. Five GFT NMR experiments were performed for resonance assignment on a Varian INOVA 600 spectrometer equipped with a cryogenic probe (total measurement time: 140 h). 97% of the backbone shifts and 13 C b resonances (excluding terminal NH 3 + , Pro 15 N, 13 C' shifts of residues preceding Pro residues), and 97% of the side chain resonances (excluding Lys NH 3 + , Arg NH 2 , OH, side chain 13 C' and aromatic quaternary 13 C) were assigned BMRB deposit with accession number 6546.

Research paper thumbnail of NMR structure of the hypothetical protein AQ1857 encoded by the Y157 gene fromAquifex aeolicus reveals a novel protein fold

Proteins-structure Function and Bioinformatics, 2004

Research paper thumbnail of NMR structure of the 18 kDa protein CC1736 from Caulobacter crescentus identifies a member of the “START” domain superfamily and suggests residues mediating substrate specificity

Proteins-structure Function and Bioinformatics, 2005

Research paper thumbnail of The second round of Critical Assessment of Automated Structure Determination of Proteins by NMR: CASD-NMR-2013

Journal of Biomolecular NMR, 2015

The second round of the community-wide initiative Critical Assessment of automated Structure Dete... more The second round of the community-wide initiative Critical Assessment of automated Structure Determination of Proteins by NMR (CASD-NMR-2013) comprised ten blind target datasets, consisting of unprocessed spectral data, assigned chemical shift lists and unassigned NOESY peak and RDC lists, that were made available in both curated (i.e. manually refined) or un-curated (i.e. automatically generated) form. Ten structure calculation programs, using fully automated protocols only, generated a total of 164 three-dimensional structures (entries) for the ten targets, sometimes using both curated and un-curated lists to generate multiple entries for a single target. The accuracy of the entries could be established by comparing them to the corresponding manually solved structure of each target, which was not available at the time the data were provided. Across the entire data set, 71 % of all entries submitted achieved an accuracy relative to the reference NMR structure better than 1.5 Å. Methods based on NOESY peak lists achieved even better results with up to 100 % of the entries within the 1.5 Å threshold for some programs. However, some methods did not converge for some targets using un-curated NOESY peak lists. Over 90 % of the entries achieved an accuracy better than the more relaxed threshold of 2.5 Å that was used in the previous CASD-NMR-2010 round. Comparisons between entries generated with un-curated versus curated peaks show only marginal improvements for the latter in those cases where both calculations converged.

Research paper thumbnail of CC1736

Research paper thumbnail of Crystal structure of RimO from Thermotoga maritima

Acta Crystallographica Section A Foundations of Crystallography, 2008

Research paper thumbnail of Solution NMR structures of immunoglobulin-like domains 7 and 12 from obscurin-like protein 1 contribute to the structural coverage of the Human Cancer Protein Interaction Network

Journal of structural and functional genomics, 2014

High-quality solution NMR structures of immunoglobulin-like domains 7 and 12 from human obscurin-... more High-quality solution NMR structures of immunoglobulin-like domains 7 and 12 from human obscurin-like protein 1 were solved. The two domains share 30% sequence identity and their structures are, as expected, rather similar. The new structures contribute to structural coverage of human cancer associated proteins. Mutations of Arg 812 in domain 7 cause the rare 3-M syndrome, and this site is located in a surface area predicted to be involved in protein-protein interactions.

Research paper thumbnail of Polypeptide backbone, Cβ and methyl group resonance assignments of the 24 kDa plectin repeat domain 6 from human protein plectin

Biomolecular NMR Assignments, 2014

The 500 kDa protein plectin is essential for the cytoskeletal organization of most mammalian cell... more The 500 kDa protein plectin is essential for the cytoskeletal organization of most mammalian cells and it is up-regulated in some types of cancer. Here, we report nearly complete sequence-specific polypeptide backbone, 13 C b and methyl group resonance assignments for 24 kDa human plectin(4403-4606) containing the C-terminal plectin repeat domain 6.

Research paper thumbnail of hydrolase domain from Pseudomonas syringae expands the structural coverage of the hydrolysis domains of class 1 peptide chain release factors

The 100-residue peptidyl-tRNA hydrolase domain from the gram-negative bacterium Pseudomonas syrin... more The 100-residue peptidyl-tRNA hydrolase domain from the gram-negative bacterium Pseudomonas syringae infecting tomato, referred to in this article as the ''P. syringae PTH domain,''(gi| 42602314, SwissProt/TrEMBL ID Q885L4_PSESM, access number Q885L4) 1 constitutes the hydrolysis domain of peptide chain release factor (RF) encoded by gene PSPTO1818. The P. syringae PTH domain has no significant amino acid sequence similarity to any protein with known three-dimensional structure, and was selected by the Protein ...

Research paper thumbnail of Structural and functional characterization of DUF1471 domains of Salmonella proteins SrfN, YdgH/SssB, and YahO

PloS one, 2014

Bacterial species in the Enterobacteriaceae typically contain multiple paralogues of a small doma... more Bacterial species in the Enterobacteriaceae typically contain multiple paralogues of a small domain of unknown function (DUF1471) from a family of conserved proteins also known as YhcN or BhsA/McbA. Proteins containing DUF1471 may have a single or three copies of this domain. Representatives of this family have been demonstrated to play roles in several cellular processes including stress response, biofilm formation, and pathogenesis. We have conducted NMR and X-ray crystallographic studies of four DUF1471 domains from Salmonella representing three different paralogous DUF1471 subfamilies: SrfN, YahO, and SssB/YdgH (two of its three DUF1471 domains: the N-terminal domain I (residues 21-91), and the C-terminal domain III (residues 244-314)). Notably, SrfN has been shown to have a role in intracellular infection by Salmonella Typhimurium. These domains share less than 35% pairwise sequence identity. Structures of all four domains show a mixed α+β fold that is most similar to that of b...

Research paper thumbnail of Supplementary Data

Research paper thumbnail of Solution structure of the free Zα domain of human DLM-1 (ZBP1/DAI), a Z-DNA binding domain

Journal of biomolecular NMR, 2014

Research paper thumbnail of Solution NMR structure of the plasmid-encoded fimbriae regulatory protein PefI from Salmonella enterica serovar Typhimurium

Proteins: Structure, Function, and Bioinformatics, 2010

Research paper thumbnail of Solution NMR structures of homeodomains from human proteins ALX4, ZHX1, and CASP8AP2 contribute to the structural coverage of the Human Cancer Protein Interaction Network

Journal of Structural and Functional Genomics, 2014

High-quality solution NMR structures of three homeodomains from human proteins ALX4, ZHX1 and CAS... more High-quality solution NMR structures of three homeodomains from human proteins ALX4, ZHX1 and CASP8AP2 were solved. These domains were chosen as targets of a biomedical theme project pursued by the Northeast Structural Genomics Consortium. This project focuses on increasing the structural coverage of human proteins associated with cancer.

Research paper thumbnail of A general computational approach for repeat protein design

Journal of molecular biology, Jan 30, 2015

Repeat proteins have considerable potential for use as modular binding reagents or biomaterials i... more Repeat proteins have considerable potential for use as modular binding reagents or biomaterials in biomedical and nanotechnology applications. Here we describe a general computational method for building idealized repeats that integrates available family sequences and structural information with Rosetta de novo protein design calculations. Idealized designs from six different repeat families were generated and experimentally characterized; 80% of the proteins were expressed and soluble and more than 40% were folded and monomeric with high thermal stability. Crystal structures determined for members of three families are within 1Å root-mean-square deviation to the design models. The method provides a general approach for fast and reliable generation of stable modular repeat protein scaffolds.

Research paper thumbnail of Crystal structure of bacterial citrate lyase

Acta Crystallographica Section A Foundations of Crystallography

Yb 3+ -co-doped YAG transparent ceramic nano-powders were prepared by carbonate altogether precip... more Yb 3+ -co-doped YAG transparent ceramic nano-powders were prepared by carbonate altogether precipitation methods, and theirstructure, morphology and properties were also analyzed by X-ray diffraction, absorption and fluorescence spectra. The results show Yb3+:YAG nano-powders are obtained with higher sintering performance and purity, and the particle shapes are regular with average diameter in the range of 100 nm. The crystalline size grew with the increase of the heat treatment temperature. The size of powder calcined at 1100ºC was about 70-150 nm, which is favorable for good sinterability of Yb3+: YAG ceramics.

Research paper thumbnail of Northeast Structural Genomics Consortium

We report NMR assignments and solution structure of the 71-residue 30S ribosomal protein S28E fro... more We report NMR assignments and solution structure of the 71-residue 30S ribosomal protein S28E from the archaean Pyrococcus horikoshii, target JR19 of the Northeast Structural Genomics Consortium. The structure, determined rapidly with the aid of automated backbone resonance assignment (AutoAssign) and automated structure determination (AutoStructure) software, is characterized by a four-stranded �-sheet with a classic Greek-key topology and an oligonucleotide/oligosaccharide �-barrel (OB) fold. The electrostatic surface of S28E exhibits positive and negative patches on opposite sides, the former constituting a putative binding site for RNA. The 13 C-terminal residues of the protein contain a consensus sequence motif constituting the signature of the S28E protein family. Surprisingly, this C-terminal segment is unstructured in solution. Keywords: Ribosomal protein; Greek-key motif; NMR structure; Northeast Structural Genomics Consortium The field of structural genomics aims at elucid...

Research paper thumbnail of A Community Resource of Experimental Data for NMR - X-ray Crystal Structure Pairs

Protein science : a publication of the Protein Society, Jan 21, 2015

We have developed an on-line NMR/X-ray Structure Pair Data Repository. The NIGMS Protein Structur... more We have developed an on-line NMR/X-ray Structure Pair Data Repository. The NIGMS Protein Structure Initiative (PSI) has provided many valuable reagents, 3D structures, and technologies for structural biology. The Northeast Structural Genomics Consortium was one of several PSI centers. NESG used both X-ray crystallography and NMR spectroscopy for protein structure determination. A key goal of the PSI was to provide experimental structures for at least one representative of each of hundreds of targeted protein domain families. In some cases, structures for identical (or nearly identical) constructs were determined by both NMR and X-ray crystallography. NMR spectroscopy and X-ray diffraction data for 41 of these "NMR/X-ray" structure pairs determined using conventional triple-resonance NMR methods with extensive sidechain resonance assignments have been organized in an on-line NMR/X-ray Structure Pair Data Repository. In addition, several NMR data sets for perdeuterated, meth...

Research paper thumbnail of The RAS-Binding Domain of Human BRAF Protein Serine/Threonine Kinase Exhibits Allosteric Conformational Changes upon Binding HRAS

Research paper thumbnail of The NMR solution structure of the 30S ribosomal protein S27e encoded in gene RS27_ARCFU of Archaeoglobus fulgidis reveals a novel protein fold

Protein Science, 2004

The Archaeoglobus fulgidis gene RS27_ARCFU encodes the 30S ribosomal protein S27e. Here, we prese... more The Archaeoglobus fulgidis gene RS27_ARCFU encodes the 30S ribosomal protein S27e. Here, we present the high-quality NMR solution structure of this archaeal protein, which comprises a C4 zinc finger motif of the CX 2 CX 14-16 CX 2 C class. S27e was selected as a target of the Northeast Structural Genomics Consortium (target ID: GR2), and its three-dimensional structure is the first representative of a family of more than 116 homologous proteins occurring in eukaryotic and archaeal cells. As a salient feature of its molecular architecture, S27e exhibits a ␤-sandwich consisting of two three-stranded sheets with topology B(↓), A(↑), F(↓), and C(↑), D(↓), E(↑). Due to the uniqueness of the arrangement of the strands, the resulting fold was found to be novel. Residues that are highly conserved among the S27 proteins allowed identification of a structural motif of putative functional importance; a conserved hydrophobic patch may well play a pivotal role for functioning of S27 proteins, be it in archaeal or eukaryotic cells. The structure of human S27, which possesses a 26-residue amino-terminal extension when compared with the archaeal S27e, was modeled on the basis of two structural templates, S27e for the carboxy-terminal core and the amino-terminal segment of the archaeal ribosomal protein L37Ae for the extension. Remarkably, the electrostatic surface properties of archaeal and human proteins are predicted to be entirely different, pointing at either functional variations among archaeal and eukaryotic S27 proteins, or, assuming that the function remained invariant, to a concerted evolutionary change of the surface potential of proteins interacting with S27.

Research paper thumbnail of GFT NMR based resonance assignment for the 21 kDa human protein UFC1

Journal of Biomolecular Nmr, 2005

Protein UFC1 (NCBI ID: 9606) is target of the Northeast Structural Genomics Consortium (ID HR41) ... more Protein UFC1 (NCBI ID: 9606) is target of the Northeast Structural Genomics Consortium (ID HR41) and belongs to a family of at least 22 homologues. Five GFT NMR experiments were performed for resonance assignment on a Varian INOVA 600 spectrometer equipped with a cryogenic probe (total measurement time: 140 h). 97% of the backbone shifts and 13 C b resonances (excluding terminal NH 3 + , Pro 15 N, 13 C' shifts of residues preceding Pro residues), and 97% of the side chain resonances (excluding Lys NH 3 + , Arg NH 2 , OH, side chain 13 C' and aromatic quaternary 13 C) were assigned BMRB deposit with accession number 6546.

Research paper thumbnail of NMR structure of the hypothetical protein AQ1857 encoded by the Y157 gene fromAquifex aeolicus reveals a novel protein fold

Proteins-structure Function and Bioinformatics, 2004

Research paper thumbnail of NMR structure of the 18 kDa protein CC1736 from Caulobacter crescentus identifies a member of the “START” domain superfamily and suggests residues mediating substrate specificity

Proteins-structure Function and Bioinformatics, 2005

Research paper thumbnail of The second round of Critical Assessment of Automated Structure Determination of Proteins by NMR: CASD-NMR-2013

Journal of Biomolecular NMR, 2015

The second round of the community-wide initiative Critical Assessment of automated Structure Dete... more The second round of the community-wide initiative Critical Assessment of automated Structure Determination of Proteins by NMR (CASD-NMR-2013) comprised ten blind target datasets, consisting of unprocessed spectral data, assigned chemical shift lists and unassigned NOESY peak and RDC lists, that were made available in both curated (i.e. manually refined) or un-curated (i.e. automatically generated) form. Ten structure calculation programs, using fully automated protocols only, generated a total of 164 three-dimensional structures (entries) for the ten targets, sometimes using both curated and un-curated lists to generate multiple entries for a single target. The accuracy of the entries could be established by comparing them to the corresponding manually solved structure of each target, which was not available at the time the data were provided. Across the entire data set, 71 % of all entries submitted achieved an accuracy relative to the reference NMR structure better than 1.5 Å. Methods based on NOESY peak lists achieved even better results with up to 100 % of the entries within the 1.5 Å threshold for some programs. However, some methods did not converge for some targets using un-curated NOESY peak lists. Over 90 % of the entries achieved an accuracy better than the more relaxed threshold of 2.5 Å that was used in the previous CASD-NMR-2010 round. Comparisons between entries generated with un-curated versus curated peaks show only marginal improvements for the latter in those cases where both calculations converged.

Research paper thumbnail of CC1736

Research paper thumbnail of Crystal structure of RimO from Thermotoga maritima

Acta Crystallographica Section A Foundations of Crystallography, 2008

Research paper thumbnail of Solution NMR structures of immunoglobulin-like domains 7 and 12 from obscurin-like protein 1 contribute to the structural coverage of the Human Cancer Protein Interaction Network

Journal of structural and functional genomics, 2014

High-quality solution NMR structures of immunoglobulin-like domains 7 and 12 from human obscurin-... more High-quality solution NMR structures of immunoglobulin-like domains 7 and 12 from human obscurin-like protein 1 were solved. The two domains share 30% sequence identity and their structures are, as expected, rather similar. The new structures contribute to structural coverage of human cancer associated proteins. Mutations of Arg 812 in domain 7 cause the rare 3-M syndrome, and this site is located in a surface area predicted to be involved in protein-protein interactions.

Research paper thumbnail of Polypeptide backbone, Cβ and methyl group resonance assignments of the 24 kDa plectin repeat domain 6 from human protein plectin

Biomolecular NMR Assignments, 2014

The 500 kDa protein plectin is essential for the cytoskeletal organization of most mammalian cell... more The 500 kDa protein plectin is essential for the cytoskeletal organization of most mammalian cells and it is up-regulated in some types of cancer. Here, we report nearly complete sequence-specific polypeptide backbone, 13 C b and methyl group resonance assignments for 24 kDa human plectin(4403-4606) containing the C-terminal plectin repeat domain 6.

Research paper thumbnail of hydrolase domain from Pseudomonas syringae expands the structural coverage of the hydrolysis domains of class 1 peptide chain release factors

The 100-residue peptidyl-tRNA hydrolase domain from the gram-negative bacterium Pseudomonas syrin... more The 100-residue peptidyl-tRNA hydrolase domain from the gram-negative bacterium Pseudomonas syringae infecting tomato, referred to in this article as the ''P. syringae PTH domain,''(gi| 42602314, SwissProt/TrEMBL ID Q885L4_PSESM, access number Q885L4) 1 constitutes the hydrolysis domain of peptide chain release factor (RF) encoded by gene PSPTO1818. The P. syringae PTH domain has no significant amino acid sequence similarity to any protein with known three-dimensional structure, and was selected by the Protein ...

Research paper thumbnail of Structural and functional characterization of DUF1471 domains of Salmonella proteins SrfN, YdgH/SssB, and YahO

PloS one, 2014

Bacterial species in the Enterobacteriaceae typically contain multiple paralogues of a small doma... more Bacterial species in the Enterobacteriaceae typically contain multiple paralogues of a small domain of unknown function (DUF1471) from a family of conserved proteins also known as YhcN or BhsA/McbA. Proteins containing DUF1471 may have a single or three copies of this domain. Representatives of this family have been demonstrated to play roles in several cellular processes including stress response, biofilm formation, and pathogenesis. We have conducted NMR and X-ray crystallographic studies of four DUF1471 domains from Salmonella representing three different paralogous DUF1471 subfamilies: SrfN, YahO, and SssB/YdgH (two of its three DUF1471 domains: the N-terminal domain I (residues 21-91), and the C-terminal domain III (residues 244-314)). Notably, SrfN has been shown to have a role in intracellular infection by Salmonella Typhimurium. These domains share less than 35% pairwise sequence identity. Structures of all four domains show a mixed α+β fold that is most similar to that of b...

Research paper thumbnail of Supplementary Data

Research paper thumbnail of Solution structure of the free Zα domain of human DLM-1 (ZBP1/DAI), a Z-DNA binding domain

Journal of biomolecular NMR, 2014

Research paper thumbnail of Solution NMR structure of the plasmid-encoded fimbriae regulatory protein PefI from Salmonella enterica serovar Typhimurium

Proteins: Structure, Function, and Bioinformatics, 2010

Research paper thumbnail of Solution NMR structures of homeodomains from human proteins ALX4, ZHX1, and CASP8AP2 contribute to the structural coverage of the Human Cancer Protein Interaction Network

Journal of Structural and Functional Genomics, 2014

High-quality solution NMR structures of three homeodomains from human proteins ALX4, ZHX1 and CAS... more High-quality solution NMR structures of three homeodomains from human proteins ALX4, ZHX1 and CASP8AP2 were solved. These domains were chosen as targets of a biomedical theme project pursued by the Northeast Structural Genomics Consortium. This project focuses on increasing the structural coverage of human proteins associated with cancer.

Research paper thumbnail of A general computational approach for repeat protein design

Journal of molecular biology, Jan 30, 2015

Repeat proteins have considerable potential for use as modular binding reagents or biomaterials i... more Repeat proteins have considerable potential for use as modular binding reagents or biomaterials in biomedical and nanotechnology applications. Here we describe a general computational method for building idealized repeats that integrates available family sequences and structural information with Rosetta de novo protein design calculations. Idealized designs from six different repeat families were generated and experimentally characterized; 80% of the proteins were expressed and soluble and more than 40% were folded and monomeric with high thermal stability. Crystal structures determined for members of three families are within 1Å root-mean-square deviation to the design models. The method provides a general approach for fast and reliable generation of stable modular repeat protein scaffolds.