Structural and functional organization of the ESCRT-I trafficking complex.
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.
Kostelansky
Michael S
MS
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.
Sun
Ji
J
Lee
Sangho
S
Kim
Jaewon
J
Ghirlando
Rodolfo
R
Hierro
Aitor
A
Emr
Scott D
SD
Hurley
James H
JH
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D056827:Endosomal Sorting Complexes Required for Transport; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010641:Phenotype; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism*
D056827:Endosomal Sorting Complexes Required for Transport; D011993:Recombinant Fusion Proteins; C115245:SRN2 protein, S cerevisiae; C425333:STP22 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C102954:VPS28 protein, S cerevisiae; D033921:Vesicular Transport Proteins