6oo2
Vps4 with Cyclic Peptide Bound in the Central Pore
Structural highlights
FunctionVPS4_YEAST Involved in the transport of biosynthetic membrane proteins from the prevacuolar/endosomal compartment to the vacuole. Required for multivesicular body (MVB) protein sorting. Catalyzes the ATP-dependent dissociation of class E VPS proteins from endosomal membranes, such as the disassembly of the ESCRT-III complex.[1] [2] [3] Publication Abstract from PubMedMany AAA+ ATPases form hexamers that unfold protein substrates by translocating them through their central pore. Multiple structures have shown how a helical assembly of subunits binds a single strand of substrate, and indicate that translocation results from the ATP-driven movement of subunits from one end of the helical assembly to the other end. To understand how more complex substrates are bound and translocated, we demonstrated that linear and cyclic versions of peptides bind to the S. cerevisiae AAA+ ATPase Vps4 with similar affinities, and determined cryo-EM structures of cyclic peptide complexes. The peptides bind in a hairpin conformation, with one primary strand equivalent to the single chain peptide ligands, while the second strand returns through the translocation pore without making intimate contacts with Vps4. These observations indicate a general mechanism by which AAA+ ATPases may translocate a variety of substrates that include extended chains, hairpins, and crosslinked polypeptide chains. Structure of Vps4 with circular peptides and implications for translocation of two polypeptide chains by AAA+ ATPases.,Han H, Fulcher JM, Dandey VP, Iwasa JH, Sundquist WI, Kay MS, Shen PS, Hill CP Elife. 2019 Jun 11;8. pii: 44071. doi: 10.7554/eLife.44071. PMID:31184588[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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