National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
R01GM032384
米国
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
S10OD021741
米国
National Institutes of Health/National Human Genome Research Institute (NIH/NHGRI)
S10OD020054
米国
引用
ジャーナル: Elife / 年: 2020 タイトル: Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction. 著者: Lan Wang / Alexander Myasnikov / Xingjie Pan / Peter Walter / 要旨: 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 ...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.
F: Membrane-spanning ATPase-like protein A: Membrane-spanning ATPase-like protein B: Membrane-spanning ATPase-like protein C: Membrane-spanning ATPase-like protein D: Membrane-spanning ATPase-like protein E: Membrane-spanning ATPase-like protein G: Unknown E. coli peptide ヘテロ分子