Dissection of the dimerization modes in the DJ-1 superfamily.
The DJ-1 superfamily (DJ-1/ThiJ/PfpI superfamily) is distributed across all three kingdoms of life. These proteins are involved in a highly diverse range of cellular functions, including chaperone and protease activity. DJ-1 proteins usually form dimers or hexamers in vivo and show at least four different binding orientations via distinct interface patches. Abnormal oligomerization of human DJ-1 is related to neurodegenerative disorders including Parkinson's disease, suggesting important functional roles of quaternary structures. However, the quaternary structures of the DJ-1 superfamily have not been extensively studied. Here, we focus on the diverse oligomerization modes among the DJ-1 superfamily proteins and investigate the functional roles of quaternary structures both computationally and experimentally. The oligomerization modes are classified into 4 types (DJ-1, YhbO, Hsp, and YDR types) depending on the distinct interface patches (I-IV) upon dimerization. A unique, rotated interface via patch I is reported, which may potentially be related to higher order oligomerization. In general, the groups based on sequence similarity are consistent with the quaternary structural classes, but their biochemical functions cannot be directly inferred using sequence information alone. The observed phyletic pattern suggests the dynamic nature of quaternary structures in the course of evolution. The amino acid residues at the interfaces tend to show lower mutation rates than those of non-interfacial surfaces.
Marine Biotechnology Research Center, Korea Ocean Research and Development Institute, Ansan, 426-744, Korea.
Hoi Jong
HJ
Jung
Sangok
S
Kim
Yun Jae
YJ
Kim
Min-Kyu
MK
Kim
Sung Gyun
SG
Kang
Jung-Hyun
JH
Lee
Wankyu
W
Kim
Sun-Shin
SS
Cha
D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D018832:Molecular Chaperones / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D059645:Mutation Rate; D015513:Oncogene Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D013329:Structure-Activity Relationship
D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1