2K3W

NMR structure of VPS4A-MIT-CHMP6

Summary for 2K3W

• Entry DOI: 10.2210/pdb2k3w/pdb
• Descriptor: Vacuolar protein sorting-associating protein 4A, Charged multivesicular body protein 6 (2 entities in total)
• Functional Keywords: esrct-iii, chmp6, mit, atp-binding, membrane, nucleotide-binding, protein transport, transport, coiled coil, endosome, lipoprotein, myristate
• Biological source: Homo sapiens (human); More
• Cellular location: Prevacuolar compartment membrane; Peripheral membrane protein: Q9UN37; Endomembrane system: Q96FZ7
• Total number of polymer chains: 2
• Total formula weight: 11700.34

Authors

Kieffer, C.,Skalicky, J.J.,Morita, E.,De Domini, I.,Ward, D.M.,Kaplan, J.,Sundquist, W.I. (deposition date: 2008-05-19, release date: 2008-10-28, Last modification date: 2024-05-29)

Primary citation

Kieffer, C.,Skalicky, J.J.,Morita, E.,De Domenico, I.,Ward, D.M.,Kaplan, J.,Sundquist, W.I.
Two distinct modes of ESCRT-III recognition are required for VPS4 functions in lysosomal protein targeting and HIV-1 budding
Dev.Cell, 15:62-73, 2008

PubMed Abstract: The ESCRT pathway mediates membrane remodeling during enveloped virus budding, cytokinesis, and intralumenal endosomal vesicle formation. Late in the pathway, a subset of membrane-associated ESCRT-III proteins display terminal amphipathic "MIM1" helices that bind and recruit VPS4 ATPases via their MIT domains. We now report that VPS4 MIT domains also bind a second, "MIM2" motif found in a different subset of ESCRT-III subunits. The solution structure of the VPS4 MIT-CHMP6 MIM2 complex revealed that MIM2 elements bind in extended conformations along the groove between the first and third helices of the MIT domain. Mutations that block VPS4 MIT-MIM2 interactions inhibit VPS4 recruitment, lysosomal protein targeting, and HIV-1 budding. MIT-MIM2 interactions appear to be common throughout the ESCRT pathway and possibly elsewhere, and we suggest how these interactions could contribute to a mechanism in which VPS4 and ESCRT-III proteins function together to constrict the necks of budding vesicles.

PubMed: 18606141
DOI: 10.1016/j.devcel.2008.05.014

Experimental method

SOLUTION NMR