Implications of the differing roles of the β1 and β3 transmembrane and cytoplasmic domains for integrin function
- Vanderbilt University Medical Center, United States
- Vanderbilt Medical Center, United States
- Virginia Tech, United States
- Max Planck Institute of Biochemistry, Germany
Abstract
Integrins are transmembrane receptors composed of α and β subunits. Although most integrins contain β1, canonical activation mechanisms are based on studies of the platelet integrin, αIIbβ3. Its inactive conformation is characterized by association of the αIIb transmembrane and cytosolic domain (TM/CT) with a tilted β3 TM/CT that leads to activation when disrupted. We show significant structural differences between β1 and β3 TM/CT in bicelles. Moreover, the 'snorkeling' lysine at the TM/CT interface of β subunits, previously proposed to regulate αIIbβ3 activation by ion pairing with nearby lipids, plays opposite roles in β1 and β3 integrin function and in neither case is responsible for TM tilt. Affinities ranging from almost no interaction to the relatively high avidity that characterizes αIIbβ3 exist between various α subunits and β1 TM/CTs. The αIIbβ3-based canonical model for the roles of the TM/CT in integrin activation and function clearly does not extend to all mammalian integrins.
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Funding
Veterans Affairs San Diego Healthcare System
- Ambra Pozzi
- Roy Zent
National Institutes of Health
- Billy G Hudson
- Ambra Pozzi
- Charles R Sanders
- Roy Zent
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2016, Lu et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Implications of the differing roles of the β1 and β3 transmembrane and cytoplasmic domains for integrin function
eLife 5:e18633.
https://doi.org/10.7554/eLife.18633
