Journal
MOLECULAR CELL
Volume 43, Issue 4, Pages 586-598Publisher
CELL PRESS
DOI: 10.1016/j.molcel.2011.07.021
Keywords
-
Categories
Funding
- Netherlands Organization for Scientific Research (NWO-ALW, NWO-ECHO)
- Netherlands Organization for Health Research and Development (ZonMw-VIDI, ZonMw-TOP)
- European Science Foundation
- Research Grants Council of Hong Kong [663808, 664009, 660709, 663610, CA07/08.SC01, HKUST6/CRF/10, AoE/B-15/01-II, SEG_HKUST06, 662710]
Ask authors/readers for more resources
Liprins are highly conserved scaffold proteins that regulate cell adhesion, cell migration, and synapse development by binding to diverse target proteins. The molecular basis governing liprin/target interactions is poorly understood. The liprin-alpha 2/CASK complex structure solved here reveals that the three SAM domains of liprin-alpha form an integrated supramodule that binds to the CASK kinase-like domain. As supported by biochemical and cellular studies, the interaction between liprin-alpha and CASK is unique to vertebrates, implying that the liprin-alpha/CASK interaction is likely to regulate higher-order brain functions in mammals. Consistently, we demonstrate that three recently identified X-linked mental retardation mutants of CASK are defective in binding to liprin-alpha. We also solved the liprin-alpha/liprin-beta SAM domain complex structure, which uncovers the mechanism underlying liprin heterodimerizaion. Finally, formation of the CASK/liprin-alpha/liprin-beta ternary complex suggests that liprins can mediate assembly of target proteins into large protein complexes capable of regulating numerous cellular activities.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available