Molecular architecture and functional model of the complete yeast ESCRT-I heterotetramer.
The endosomal sorting complex required for transport-I (ESCRT-I) complex, which is conserved from yeast to humans, directs the lysosomal degradation of ubiquitinated transmembrane proteins and the budding of the HIV virus. Yeast ESCRT-I contains four subunits, Vps23, Vps28, Vps37, and Mvb12. The crystal structure of the heterotetrameric ESCRT-I complex reveals a highly asymmetric complex of 1:1:1:1 subunit stoichiometry. The core complex is nearly 18 nm long and consists of a headpiece attached to a 13 nm stalk. The stalk is important for cargo sorting by ESCRT-I and is proposed to serve as a spacer regulating the correct disposition of cargo and other ESCRT components. Hydrodynamic constraints and crystallographic structures were used to generate a model of intact ESCRT-I in solution. The results show how ESCRT-I uses a combination of a rigid stalk and flexible tethers to interact with lipids, cargo, and other ESCRT complexes over a span of approximately 25 nm.
Kostelansky
Michael S
MS
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20892, USA.
Schluter
Cayetana
C
Tam
Yuen Yi C
YY
Lee
Sangho
S
Ghirlando
Rodolfo
R
Beach
Bridgette
B
Conibear
Elizabeth
E
Hurley
James H
JH
D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000378:metabolism
D056827:Endosomal Sorting Complexes Required for Transport; D046912:Multiprotein Complexes; C517100:Mvb12 protein, S cerevisiae; C115245:SRN2 protein, S cerevisiae; C425333:STP22 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C102954:VPS28 protein, S cerevisiae; D033921:Vesicular Transport Proteins