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Title: Structural and Biochemical Studies of ALIX/AlP1 and Its Role in Retrovirus Budding

Abstract

ALIX/AIP1 functions in enveloped virus budding, endosomal protein sorting, and many other cellular processes. Retroviruses, including HIV-1, SIV, and EIAV, bind and recruit ALIX through YPXnL late-domain motifs (X = any residue; n = 1-3). Crystal structures reveal that human ALIX is composed of an N-terminal Bro1 domain and a central domain that is composed of two extended three-helix bundles that form elongated arms that fold back into a 'V.'. The structures also reveal conformational flexibility in the arms that suggests that the V domain may act as a flexible hinge in response to ligand binding. YPXnL late domains bind in a conserved hydrophobic pocket on the second arm near the apex of the V, whereas CHMP4/ESCRT-III proteins bind a conserved hydrophobic patch on the Bro1 domain, and both interactions are required for virus budding. ALIX therefore serves as a flexible, extended scaffold that connects retroviral Gag proteins to ESCRT-III and other cellular-budding machinery.

Authors:
; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930396
Report Number(s):
BNL-81118-2008-JA
Journal ID: ISSN 0092-8674; CELLB5; TRN: US200904%%676
DOE Contract Number:  
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Cell; Journal Volume: 128
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; AIDS VIRUS; CRYSTAL STRUCTURE; FLEXIBILITY; PROTEINS; SIMIAN VIRUS; SORTING; VIRAL DISEASES; national synchrotron light source

Citation Formats

Fisher,R., Chung, H., Zhai, Q., Robinson, H., Sundquist, W., and Hill, C.. Structural and Biochemical Studies of ALIX/AlP1 and Its Role in Retrovirus Budding. United States: N. p., 2007. Web. doi:10.1016/j.cell.2007.01.035.
Fisher,R., Chung, H., Zhai, Q., Robinson, H., Sundquist, W., & Hill, C.. Structural and Biochemical Studies of ALIX/AlP1 and Its Role in Retrovirus Budding. United States. doi:10.1016/j.cell.2007.01.035.
Fisher,R., Chung, H., Zhai, Q., Robinson, H., Sundquist, W., and Hill, C.. Mon . "Structural and Biochemical Studies of ALIX/AlP1 and Its Role in Retrovirus Budding". United States. doi:10.1016/j.cell.2007.01.035.
@article{osti_930396,
title = {Structural and Biochemical Studies of ALIX/AlP1 and Its Role in Retrovirus Budding},
author = {Fisher,R. and Chung, H. and Zhai, Q. and Robinson, H. and Sundquist, W. and Hill, C.},
abstractNote = {ALIX/AIP1 functions in enveloped virus budding, endosomal protein sorting, and many other cellular processes. Retroviruses, including HIV-1, SIV, and EIAV, bind and recruit ALIX through YPXnL late-domain motifs (X = any residue; n = 1-3). Crystal structures reveal that human ALIX is composed of an N-terminal Bro1 domain and a central domain that is composed of two extended three-helix bundles that form elongated arms that fold back into a 'V.'. The structures also reveal conformational flexibility in the arms that suggests that the V domain may act as a flexible hinge in response to ligand binding. YPXnL late domains bind in a conserved hydrophobic pocket on the second arm near the apex of the V, whereas CHMP4/ESCRT-III proteins bind a conserved hydrophobic patch on the Bro1 domain, and both interactions are required for virus budding. ALIX therefore serves as a flexible, extended scaffold that connects retroviral Gag proteins to ESCRT-III and other cellular-budding machinery.},
doi = {10.1016/j.cell.2007.01.035},
journal = {Cell},
number = ,
volume = 128,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}