6PE0

Msp1 (E214Q)-substrate complex

Summary for 6PE0

• Entry DOI: 10.2210/pdb6pe0/pdb
• EMDB information: 20318 20320
• Descriptor: Membrane-spanning ATPase-like protein, Unknown E. coli peptide, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: membrane protein, tail-anchored protein, protein quality control, protein transport
• Biological source: Chaetomium thermophilum; More
• Total number of polymer chains: 7
• Total formula weight: 259115.50

Authors

Wang, L.,Myasnikov, A.,Pan, X.,Walter, P. (deposition date: 2019-06-19, release date: 2020-02-12, Last modification date: 2024-03-20)

Primary citation

Wang, L.,Myasnikov, A.,Pan, X.,Walter, P.
Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction.
Elife, 9:-, 2020

PubMed Abstract: The AAA protein Msp1 extracts mislocalized tail-anchored membrane proteins and targets them for degradation, thus maintaining proper cell organization. How Msp1 selects its substrates and firmly engages them during the energetically unfavorable extraction process remains a mystery. To address this question, we solved cryo-EM structures of Msp1-substrate complexes at near-atomic resolution. Akin to other AAA proteins, Msp1 forms hexameric spirals that translocate substrates through a central pore. A singular hydrophobic substrate recruitment site is exposed at the spiral's seam, which we propose positions the substrate for entry into the pore. There, a tight web of aromatic amino acids grips the substrate in a sequence-promiscuous, hydrophobic milieu. Elements at the intersubunit interfaces coordinate ATP hydrolysis with the subunits' positions in the spiral. We present a comprehensive model of Msp1's mechanism, which follows general architectural principles established for other AAA proteins yet specializes Msp1 for its unique role in membrane protein extraction.

PubMed: 31999255
DOI: 10.7554/eLife.54031

Experimental method

ELECTRON MICROSCOPY (3.5 Å)