Crystal Structure of the Complete Integrin αVβ3 Ectodomain Plus an α/β Transmembrane Fragment
View/ Open
Author
Mahalingham, Bhuvaneshwari
Borrelli, Laura Ann
Rysiok, Thomas
Müller-Pompalla, Dirk
Goodman, Simon L.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1083/jcb.200905085Metadata
Show full item recordCitation
Xiong, Jian-Ping, Bhuvaneshwari Mahalingham, Jose Luis Alonso, Laura Ann Borrelli, Xianliang Rui, Saurabh Anand, Bradley T. Hyman, et al. 2009. Crystal structure of the complete integrin αVβ3 ectodomain plus an α/β transmembrane fragment. The Journal of Cell Biology 186(4): 589-600.Abstract
We determined the crystal structure of 1TM-αVβ3, which represents the complete unconstrained ectodomain plus short C-terminal transmembrane stretches of the αV and β3 subunits. 1TM-αVβ3 is more compact and less active in solution when compared with ΔTM-αVβ3, which lacks the short C-terminal stretches. The structure reveals a bent conformation and defines the α–β interface between IE2 (EGF-like 2) and the thigh domains. Modifying this interface by site-directed mutagenesis leads to robust integrin activation. Fluorescent lifetime imaging microscopy of inactive full-length αVβ3 on live cells yields a donor–membrane acceptor distance, which is consistent with the bent conformation and does not change in the activated integrin. These data are the first direct demonstration of conformational coupling of the integrin leg and head domains, identify the IE2–thigh interface as a critical steric barrier in integrin activation, and suggest that inside-out activation in intact cells may involve conformational changes other than the postulated switch to a genu-linear state.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2733745/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:5352099
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)