Crystal structure of human vacuolar protein sorting protein 29 reveals a phosphodiesterase/nuclease-like fold and two protein-protein interaction sites.
Vacuolar protein sorting protein 29 (Vps29p), which is involved in retrograde trafficking from prevacuolar endosomes to the trans-Golgi network, performs its biological functions by participating in the formation of a "retromer complex." In human cells, this complex comprises four conserved proteins: hVps35p, hVps29p, hVps26p, and sorting nexin 1 protein (SNX1). Here, we report the crystal structure of hVps29p at 2.1 Angstroms resolution, the first three-dimensional structure of the retromer subunits. This novel structure adopts a four-layered alpha-beta-beta-alpha sandwich fold. hVps29p contains a metal-binding site that is very similar to the active sites of some proteins of the phosphodiesterase/nuclease protein family, indicating that hVps29p may carry out chemically similar functions. Structure and sequence conservation analysis suggests that hVps29p contains two protein-protein interaction sites. One site, which potentially serves as the interface between hVps29p and hVps35p, comprises 5 conserved hydrophobic and 8 hydrophilic residues. The other site is relatively more hydrophilic and may serve as a binding interface with hVps26p, SNX1, or other target proteins.
Wang
Deqiang
D
Hefei National Laboratory of Physical Sciences at Microscale, Key Laboratory of Structural Biology of Chinese Academy of Sciences.
Guo
Min
M
Liang
Zhi
Z
Fan
Jun
J
Zhu
Zhiqiang
Z
Zang
Jianye
J
Zhu
Zhongliang
Z
Li
Xiaowu
X
Teng
Maikun
M
Niu
Liwen
L
Dong
Yuhui
Y
Liu
Peng
P
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D033921:Vesicular Transport Proteins / Q000737:chemistry; D021601:trans-Golgi Network / Q000378:metabolism
D002352:Carrier Proteins; D018076:DNA, Complementary; C419572:VPS29 protein, human; D033921:Vesicular Transport Proteins