5T0G

Structural basis for dynamic regulation of the human 26S proteasome

Summary for 5T0G

• Entry DOI: 10.2210/pdb5t0g/pdb
• Related: 5T0C 5T0H 5T0I 5T0J
• EMDB information: 8332 8333 8334 8335 8336 8337
• Descriptor: Proteasome subunit alpha type-6, Proteasome subunit beta type-3, Proteasome subunit beta type-2, ... (34 entities in total)
• Functional Keywords: ubiquitin-proteasome system, aaa-atpase, hydrolase
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm: P60900 P49720 P49721 P28074 P20618 P28070 P35998 P62191 P43686 P17980 P25787 P62195 P25789 O14818 P28066 P25786 P25788 P28072 Q99436; Nucleus : O00231
• Total number of polymer chains: 32
• Total formula weight: 1266701.16

Authors

Chen, S.,Wu, J.,Lu, Y.,Ma, Y.B.,Lee, B.H.,Yu, Z.,Ouyang, Q.,Finley, D.,Kirschner, M.W.,Mao, Y. (deposition date: 2016-08-16, release date: 2016-10-19, Last modification date: 2024-10-23)

Primary citation

Chen, S.,Wu, J.,Lu, Y.,Ma, Y.B.,Lee, B.H.,Yu, Z.,Ouyang, Q.,Finley, D.J.,Kirschner, M.W.,Mao, Y.
Structural basis for dynamic regulation of the human 26S proteasome.
Proc.Natl.Acad.Sci.USA, 113:12991-12996, 2016

PubMed Abstract: The proteasome is the major engine of protein degradation in all eukaryotic cells. At the heart of this machine is a heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitylated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides. Using cryoelectron microscopy, we determined a near-atomic-resolution structure of the 2.5-MDa human proteasome in its ground state, as well as subnanometer-resolution structures of the holoenzyme in three alternative conformational states. The substrate-unfolding AAA-ATPase channel is narrowed by 10 inward-facing pore loops arranged into two helices that run in parallel with each other, one hydrophobic in character and the other highly charged. The gate of the core particle was unexpectedly found closed in the ground state and open in only one of the alternative states. Coordinated, stepwise conformational changes of the regulatory particle couple ATP hydrolysis to substrate translocation and regulate gating of the core particle, leading to processive degradation.

PubMed: 27791164
DOI: 10.1073/pnas.1614614113

Experimental method

ELECTRON MICROSCOPY (4.4 Å)