Protein structure prediction for the male-specific region of the human Y chromosome - PubMed (original) (raw)

Protein structure prediction for the male-specific region of the human Y chromosome

Krzysztof Ginalski et al. Proc Natl Acad Sci U S A. 2004.

Abstract

The complete sequence of the male-specific region of the human Y chromosome (MSY) has been determined recently; however, detailed characterization for many of its encoded proteins still remains to be done. We applied state-of-the-art protein structure prediction methods to all 27 distinct MSY-encoded proteins to provide better understanding of their biological functions and their mechanisms of action at the molecular level. The results of such large-scale structure-functional annotation provide a comprehensive view of the MSY proteome, shedding light on MSY-related processes. We found that, in total, at least 60 domains are encoded by 27 distinct MSY genes, of which 42 (70%) were reliably mapped to currently known structures. The most challenging predictions include the unexpected but confident 3D structure assignments for three domains identified here encoded by the USP9Y, UTY, and BPY2 genes. The domains with unknown 3D structures that are not predictable with currently available theoretical methods are established as primary targets for crystallographic or NMR studies. The data presented here set up the basis for additional scientific discoveries in human biology of the Y chromosome, which plays a fundamental role in sex determination.

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Figures

Fig. 1.

Fig. 1.

Summary of structure prediction for the complete set of proteins encoded by 27 distinct MSY genes. The following classes together with the number and the percentage of encompassed amino acids are presented: 3D structure assigned with

pdb

-

blast

; 3D structure assigned with SMART/CDD; 3D structure assigned with FR/AI methods; structured regions with clear secondary structure prediction patterns but not annotated at the 3D level (include separate domains as well as regions that possibly pack on the neighboring domains); transmembrane regions; unstructured nonglobular regions; and other, remaining regions encompassing segments <30 residues (mainly linkers between domains) and regions that could not be assigned with confidence to any of the former classes.

Fig. 2.

Fig. 2.

THe C-terminal domain of UTY is a treble-clef zinc finger. (a)

rosetta

3D model of C-terminal domain of UTY (GI:2580574). The side chains of Cys-1278, Cys-1281, Cys-1305, and Cys-1308 that are predicted to take part in coordination of zinc ion are shown. (b) Similar structure of Rattus norvegicus effector domain of Rabphilin-3A (PDB ID code 1zbd) (39) selected independently with the 3

d

-

jury

method. Cys-94, Cys-97, Cys-119, and Cys-122 side chains, as well as coordinated zinc ion (orange), are presented. (c) The sequence alignment of representative sequences belonging to UTY and Rabphilin-3A families. Regions that could not be aligned with confidence by using the consensus alignment approach and 3D assessment, as well as those that may not be structurally conserved, are not shown. The numbers in square brackets specify the number of excluded residues. Uncharged residues in mostly hydrophobic sites are highlighted in yellow, polar residues at mostly hydrophilic sites are highlighted in light gray, and small residues at positions occupied by mostly small residues are shown in red letters. Conserved cysteine residues forming a zinc-binding site are highlighted in black. Locations of the secondary structure elements in UTY (consensus of secondary structure predictions) and Rabphilin-3A are marked above the sequences. The color shading of secondary structure elements corresponds to those in the respective structural diagrams. Secondary structure elements not shown in the alignment panel but presented in structural diagrams are colored white. The same presentation scheme is used for Figs. 3 and 4.

Fig. 3.

Fig. 3.

USP9Y encloses the domain that belongs to the superfamily of ubiquitin-like proteins. (a)

rosetta

3D model of the β-grasp (ubiquitin-like) domain of USP9Y (GI:2580558). (b) Similar structure of Arabidopsis thaliana ubiquitin-like protein 7 (Rub1) (PDB ID code 1bt0) (40) selected independently with the 3

d

-

jury

method. (c) The sequence alignment of representative sequences belonging to USP9Y and Rub1 families.

Fig. 4.

Fig. 4.

BPY2 forms a winged HTH-like structure. (a)

rosetta

3D model of BPY2 (GI:2580546). (b) Similar structure of Escherichia coli N-terminal DNA-binding domain of arginine repressor (PDB ID code 1aoy) (37) selected independently with the 3

d

-

jury

method. (c) The sequence alignment of BPY2 and representative sequences belonging to the arginine repressor family. The turn in an HTH-like motif is shown in red.

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