2xs1
From Proteopedia
Crystal Structure of ALIX in complex with the SIVmac239 PYKEVTEDL Late Domain
Structural highlights
FunctionPDC6I_HUMAN Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and enveloped virus budding (HIV-1 and other lentiviruses). Appears to be an adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function implies the interaction with CHMP4B. May play a role in the regulation of both apoptosis and cell proliferation.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedRetroviral Gag proteins contain short late domain motifs that recruit cellular ESCRT pathway proteins to facilitate virus budding. ALIX-binding late domains often contain the core consensus sequence: "YPXnL" (where Xn can vary in sequence and length). However, some SIV Gag proteins lack this consensus sequence, yet still bind ALIX. We mapped divergent, ALIX-binding late domains within the p6(Gag) proteins of SIVmac239 (40SREKPYKEVTEDLLHLNSLF59) and SIVagmTan-1 (24AAGAYDPARKLLEQYAKK41). Crystal structures revealed that anchoring tyrosines (bold) and nearby hydrophobic residues (underlined) contact the ALIX V domain, revealing how lentiviruses employ a diverse family of late domain sequences to bind ALIX and promote virus budding. Identification and Structural Characterization of the ALIX-Binding Late Domains of SIVmac239 and SIVagmTan-1.,Zhai Q, Landesman M, Robinson H, Sundquist WI, Hill CP J Virol. 2010 Oct 20. PMID:20962096[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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