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6msb

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Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome

6msb, resolution 3.00Å

Structural highlights

6msb is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3Å
Ligands:
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PSMD1_HUMAN Acts as a regulatory subunit of the 26 proteasome which is involved in the ATP-dependent degradation of ubiquitinated proteins.

Publication Abstract from PubMed

The proteasome is an ATP-dependent, 2.5-megadalton machine responsible for selective protein degradation in eukaryotic cells. Here we present cryo-EM structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 A resolution, captured during breakdown of a polyubiquitylated protein. These structures visualize a continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. Three principal modes of coordinated hydrolysis are observed, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases, and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, translocation initiation and processive unfolding of substrates, respectively. ATP hydrolysis powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate.

Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome.,Dong Y, Zhang S, Wu Z, Li X, Wang WL, Zhu Y, Stoilova-McPhie S, Lu Y, Finley D, Mao Y Nature. 2018 Nov 12. pii: 10.1038/s41586-018-0736-4. doi:, 10.1038/s41586-018-0736-4. PMID:30479383^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Dong Y, Zhang S, Wu Z, Li X, Wang WL, Zhu Y, Stoilova-McPhie S, Lu Y, Finley D, Mao Y. Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome. Nature. 2018 Nov 12. pii: 10.1038/s41586-018-0736-4. doi:, 10.1038/s41586-018-0736-4. PMID:30479383 doi:http://dx.doi.org/10.1038/s41586-018-0736-4