structure of the bro1 domain protein brox and functional analyses of the alix bro1 domain in hiv-1 buddingbro1结构域蛋白质brox和功能分析的阿历克斯bro1域在hiv - 1萌芽.pdfVIP

Structure of the Bro1 Domain Protein BROX and Functional Analyses of the ALIX Bro1 Domain in HIV-1 Budding 1. 1. 2 1 Qianting Zhai , Michael B. Landesman , Howard Robinson , Wesley I. Sundquist *, Christopher P. Hill1* 1 Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah, United States of America, 2 Department of Biology, Brookhaven National Laboratory, Upton, New York, United States of America Abstract Background: Bro1 domains are elongated, banana-shaped domains that were first identified in the yeast ESCRT pathway protein, Bro1p. Humans express three Bro1 domain-containing proteins: ALIX, BROX, and HD-PTP, which function in association with the ESCRT pathway to help mediate intraluminal vesicle formation at multivesicular bodies, the abscission stage of cytokinesis, and/or enveloped virus budding. Human Bro1 domains share the ability to bind the CHMP4 subset of ESCRT-III proteins, associate with the HIV-1 NCGag protein, and stimulate the budding of viral Gag proteins. The curved Bro1 domain structure has also been proposed to mediate membrane bending. To date, crystal structures have only been available for the related Bro1 domains from the Bro1p and ALIX proteins, and structures of additional family members should therefore aid in the identification of key structural and functional elements. Methodology/Principal Findings: We report the crystal structure of the human BROX protein, which comprises a single Bro1 domain. The Bro1 domains from BROX, Bro1p and ALIX adopt similar overall structures and sha