M. Landau - Academia.edu (original) (raw)

Papers by M. Landau

Journal of Biological Chemistry, 2014

Background: Amyloid fibers are protein aggregates associated with numerous pathologies. Results: ... more Background: Amyloid fibers are protein aggregates associated with numerous pathologies. Results: Mcg light chain variable domains form amyloid fibers through monomers. Conclusion: This light chain variable domain monomer is the fundamental unit required to form amyloid fibers. Significance: Understanding the molecular mechanism of Mcg light chain amyloid fiber formation has implications for treating systemic amyloidosis.

Nucleic Acids Research, 2005

Key amino acid positions that are important for maintaining the 3D structure of a protein and/or ... more Key amino acid positions that are important for maintaining the 3D structure of a protein and/or its function(s), e.g. catalytic activity, binding to ligand, DNA or other proteins, are often under strong evolutionary constraints. Thus, the biological importance of a residue often correlates with its level of evolutionary conservation within the protein family. ConSurf (http://consurf.tau.ac.il/) is a web-based tool that automatically calculates evolutionary conservation scores and maps them on protein structures via a user-friendly interface. Structurally and functionally important regions in the protein typically appear as patches of evolutionarily conserved residues that are spatially close to each other. We present here version 3.0 of ConSurf. This new version includes an empirical Bayesian method for scoring conservation, which is more accurate than the maximum-likelihood method that was used in the earlier release. Various additional steps in the calculation can now be controlled by a number of advanced options, thus further improving the accuracy of the calculation. Moreover, ConSurf version 3.0 also includes a measure of confidence for the inferred amino acid conservation scores.

Protein Science, 2010

Small heat shock proteins alphaA and alphaB crystallin form highly polydisperse oligomers that fr... more Small heat shock proteins alphaA and alphaB crystallin form highly polydisperse oligomers that frustrate protein aggregation, crystallization, and amyloid formation. Here, we present the crystal structures of truncated forms of bovine alphaA crystallin (AAC 59-163) and human alphaB crystallin (ABC 68-162), both containing the C-terminal extension that functions in chaperone action and oligomeric assembly. In both structures, the C-terminal extensions swap into neighboring molecules, creating runaway domain swaps. This interface, termed DS, enables crystallin polydispersity because the C-terminal extension is palindromic and thereby allows the formation of equivalent residue interactions in both directions. That is, we observe that the extension binds in opposite directions at the DS interfaces of AAC 59-163 and ABC 68-162. A second dimeric interface, termed AP, also enables polydispersity by forming an antiparallel beta sheet with three distinct registration shifts. These two polymorphic interfaces enforce polydispersity of alpha crystallin. This evolved polydispersity suggests molecular mechanisms for chaperone action and for prevention of crystallization, both necessary for transparency of eye lenses.

The Journal of biological chemistry, Jan 3, 2014

Systemic light chain amyloidosis is a lethal disease characterized by excess immunoglobulin light... more Systemic light chain amyloidosis is a lethal disease characterized by excess immunoglobulin light chains and light chain fragments composed of variable domains, which aggregate into amyloid fibers. These fibers accumulate and damage organs. Some light chains induce formation of amyloid fibers, whereas others do not, making it unclear what distinguishes amyloid formers from non-formers. One mechanism by which sequence variation may reduce propensity to form amyloid fibers is by shifting the equilibrium toward an amyloid-resistant quaternary structure. Here we identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers.

Journal of Thrombosis and Haemostasis, 2004

To cite this article: Rosenberg N, Landau M, Luboshitz J, Rechavi G, Seligsohn U. A novel Phe171C... more To cite this article: Rosenberg N, Landau M, Luboshitz J, Rechavi G, Seligsohn U. A novel Phe171Cys mutation in integrin a IIb causes Glanzmann thrombasthenia by abrogating a IIb b 3 complex formation. J Thromb Haemost 2004; 2: 1167-75. essential role in the interface between the b-propeller domain of a IIb and the bA domain of b 3 . Conclusions: A novel Phe171Cys mutation in the a IIb gene of patients with GT is associated with abrogation of a IIb b 3 complex formation.

Journal of Thrombosis and Haemostasis, 2007

Trp207Gly in platelet glycoprotein Iba is a novel mutation that disrupts the connection between t... more Trp207Gly in platelet glycoprotein Iba is a novel mutation that disrupts the connection between the leucine-rich repeat domain and the disulfide loop structure and causes Bernard-Soulier syndrome To cite this article: Rosenberg N, Lalezari S, Landau M, Shenkman B, Seligsohn U, Izraeli S. Trp207Gly in platelet glycoprotein Iba is a novel mutation that disrupts the connection between the leucine-rich repeat domain and the disulfide loop structure and causes Bernard-Soulier syndrome. J Thromb Haemost 2007; 5: 378-86.

Proceedings of the National Academy of Sciences, 2011

Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmar... more Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. Aβ molecules form β-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of Aβ has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate Aβ polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of Aβ. These structures, all of short, self-complementing pairs of β-sheets termed steric zippers, reveal a variety of modes of self-association of Aβ. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to Aβ. These structures and molecular models contribute fundamental information for understanding Aβ polymorphic nature and pathogenesis.

Journal of Biological Chemistry, 2014

Background: Amyloid fibers are protein aggregates associated with numerous pathologies. Results: ... more Background: Amyloid fibers are protein aggregates associated with numerous pathologies. Results: Mcg light chain variable domains form amyloid fibers through monomers. Conclusion: This light chain variable domain monomer is the fundamental unit required to form amyloid fibers. Significance: Understanding the molecular mechanism of Mcg light chain amyloid fiber formation has implications for treating systemic amyloidosis.

Nucleic Acids Research, 2005

Key amino acid positions that are important for maintaining the 3D structure of a protein and/or ... more Key amino acid positions that are important for maintaining the 3D structure of a protein and/or its function(s), e.g. catalytic activity, binding to ligand, DNA or other proteins, are often under strong evolutionary constraints. Thus, the biological importance of a residue often correlates with its level of evolutionary conservation within the protein family. ConSurf (http://consurf.tau.ac.il/) is a web-based tool that automatically calculates evolutionary conservation scores and maps them on protein structures via a user-friendly interface. Structurally and functionally important regions in the protein typically appear as patches of evolutionarily conserved residues that are spatially close to each other. We present here version 3.0 of ConSurf. This new version includes an empirical Bayesian method for scoring conservation, which is more accurate than the maximum-likelihood method that was used in the earlier release. Various additional steps in the calculation can now be controlled by a number of advanced options, thus further improving the accuracy of the calculation. Moreover, ConSurf version 3.0 also includes a measure of confidence for the inferred amino acid conservation scores.

Protein Science, 2010

Small heat shock proteins alphaA and alphaB crystallin form highly polydisperse oligomers that fr... more Small heat shock proteins alphaA and alphaB crystallin form highly polydisperse oligomers that frustrate protein aggregation, crystallization, and amyloid formation. Here, we present the crystal structures of truncated forms of bovine alphaA crystallin (AAC 59-163) and human alphaB crystallin (ABC 68-162), both containing the C-terminal extension that functions in chaperone action and oligomeric assembly. In both structures, the C-terminal extensions swap into neighboring molecules, creating runaway domain swaps. This interface, termed DS, enables crystallin polydispersity because the C-terminal extension is palindromic and thereby allows the formation of equivalent residue interactions in both directions. That is, we observe that the extension binds in opposite directions at the DS interfaces of AAC 59-163 and ABC 68-162. A second dimeric interface, termed AP, also enables polydispersity by forming an antiparallel beta sheet with three distinct registration shifts. These two polymorphic interfaces enforce polydispersity of alpha crystallin. This evolved polydispersity suggests molecular mechanisms for chaperone action and for prevention of crystallization, both necessary for transparency of eye lenses.

The Journal of biological chemistry, Jan 3, 2014

Systemic light chain amyloidosis is a lethal disease characterized by excess immunoglobulin light... more Systemic light chain amyloidosis is a lethal disease characterized by excess immunoglobulin light chains and light chain fragments composed of variable domains, which aggregate into amyloid fibers. These fibers accumulate and damage organs. Some light chains induce formation of amyloid fibers, whereas others do not, making it unclear what distinguishes amyloid formers from non-formers. One mechanism by which sequence variation may reduce propensity to form amyloid fibers is by shifting the equilibrium toward an amyloid-resistant quaternary structure. Here we identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers.

Journal of Thrombosis and Haemostasis, 2004

To cite this article: Rosenberg N, Landau M, Luboshitz J, Rechavi G, Seligsohn U. A novel Phe171C... more To cite this article: Rosenberg N, Landau M, Luboshitz J, Rechavi G, Seligsohn U. A novel Phe171Cys mutation in integrin a IIb causes Glanzmann thrombasthenia by abrogating a IIb b 3 complex formation. J Thromb Haemost 2004; 2: 1167-75. essential role in the interface between the b-propeller domain of a IIb and the bA domain of b 3 . Conclusions: A novel Phe171Cys mutation in the a IIb gene of patients with GT is associated with abrogation of a IIb b 3 complex formation.

Journal of Thrombosis and Haemostasis, 2007

Trp207Gly in platelet glycoprotein Iba is a novel mutation that disrupts the connection between t... more Trp207Gly in platelet glycoprotein Iba is a novel mutation that disrupts the connection between the leucine-rich repeat domain and the disulfide loop structure and causes Bernard-Soulier syndrome To cite this article: Rosenberg N, Lalezari S, Landau M, Shenkman B, Seligsohn U, Izraeli S. Trp207Gly in platelet glycoprotein Iba is a novel mutation that disrupts the connection between the leucine-rich repeat domain and the disulfide loop structure and causes Bernard-Soulier syndrome. J Thromb Haemost 2007; 5: 378-86.

Proceedings of the National Academy of Sciences, 2011

Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmar... more Amyloid-beta (Aβ) aggregates are the main constituent of senile plaques, the histological hallmark of Alzheimer's disease. Aβ molecules form β-sheet containing structures that assemble into a variety of polymorphic oligomers, protofibers, and fibers that exhibit a range of lifetimes and cellular toxicities. This polymorphic nature of Aβ has frustrated its biophysical characterization, its structural determination, and our understanding of its pathological mechanism. To elucidate Aβ polymorphism in atomic detail, we determined eight new microcrystal structures of fiber-forming segments of Aβ. These structures, all of short, self-complementing pairs of β-sheets termed steric zippers, reveal a variety of modes of self-association of Aβ. Combining these atomic structures with previous NMR studies allows us to propose several fiber models, offering molecular models for some of the repertoire of polydisperse structures accessible to Aβ. These structures and molecular models contribute fundamental information for understanding Aβ polymorphic nature and pathogenesis.