Structural and Functional Organization of the ESCRT-I Trafficking Complex

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2006.01.049 Byline: Michael S. Kostelansky (1), Ji Sun (2), Sangho Lee (1), Jaewon Kim (1), Rodolfo Ghirlando (1), Aitor Hierro (1), Scott D. Emr (2), James H. Hurley (1) Abstract: The endosomal sorting complex required for transport (ESCRT) complexes are central to receptor downregulation, lysosome biogenesis, and budding of HIV. The yeast ESCRT-I complex contains the Vps23, Vps28, and Vps37 proteins, and its assembly is directed by the C-terminal steadiness box of Vps23, the N-terminal half of Vps28, and the C-terminal half of Vps37. The crystal structures of a Vps23:Vps28 core subcomplex and the Vps23:Vps28:Vps37 core were solved at 2.1 and 2.8 A resolution. Each subunit contains a structurally similar pair of helices that form the core. The N-terminal domain of Vps28 has a hydrophobic binding site on its surface that is conformationally dynamic. The C-terminal domain of Vps28 binds the ESCRT-II complex. The structure shows how ESCRT-I is assembled by a compact core from which the Vps23 UEV domain, the Vps28 C domain, and other domains project to bind their partners. Author Affiliation: (1) Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services, Bethesda, MD 20892, USA (2) Department of Cellular and Molecular Medicine, Department of Chemistry and Biochemistry, and Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA Article History: Received 27 September 2005; Revised 6 December 2005; Accepted 12 January 2006 Article Note: (miscellaneous) Published: April 6, 2006