Structural highlights
Function
PRS7_HUMAN The 26S protease is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex. In case of HIV-1 infection, positive modulator of Tat-mediated transactivation.[1]
Publication Abstract from PubMed
The proteasome holoenzyme is activated by its regulatory particle (RP) consisting of two subcomplexes, the lid and the base. A key event in base assembly is the formation of a heterohexameric ring of AAA-ATPases, which is guided by at least four RP assembly chaperones in mammals: PAAF1, p28/gankyrin, p27/PSMD9, and S5b. Using cryogenic electron microscopy, we analyzed the non-AAA structure of the p28-bound human RP at 4.5 A resolution and determined seven distinct conformations of the Rpn1-p28-AAA subcomplex within the p28-bound RP at subnanometer resolutions. Remarkably, the p28-bound AAA ring does not form a channel in the free RP and spontaneously samples multiple "open" and "closed" topologies at the Rpt2-Rpt6 and Rpt3-Rpt4 interfaces. Our analysis suggests that p28 assists the proteolytic core particle to select a specific conformation of the ATPase ring for RP engagement and is released in a shoehorn-like fashion in the last step of the chaperone-mediated proteasome assembly.
Conformational Landscape of the p28-Bound Human Proteasome Regulatory Particle.,Lu Y, Wu J, Dong Y, Chen S, Sun S, Ma YB, Ouyang Q, Finley D, Kirschner MW, Mao Y Mol Cell. 2017 Jul 20;67(2):322-333.e6. doi: 10.1016/j.molcel.2017.06.007. Epub, 2017 Jul 6. PMID:28689658[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Chen Y, Sharp ZD, Lee WH. HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins. J Biol Chem. 1997 Sep 19;272(38):24081-7. PMID:9295362
- ↑ Lu Y, Wu J, Dong Y, Chen S, Sun S, Ma YB, Ouyang Q, Finley D, Kirschner MW, Mao Y. Conformational Landscape of the p28-Bound Human Proteasome Regulatory Particle. Mol Cell. 2017 Jul 20;67(2):322-333.e6. doi: 10.1016/j.molcel.2017.06.007. Epub, 2017 Jul 6. PMID:28689658 doi:http://dx.doi.org/10.1016/j.molcel.2017.06.007
