期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 107, 期 41, 页码 17592-17597出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1011247107
关键词
cis trans interfaces; cell adhesion; intercellular signaling
资金
- National Science Foundation [MCB-0918535]
- National Institutes of Health [R01 GM062270-07]
- US-Israel Binational Science Foundation [2006-401]
- Israel Science Foundation [659/06]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [918535] Funding Source: National Science Foundation
Intercellullar junctions formed by cadherins, including desmosomes and adherens junctions, comprise two dimensional arrays of trans dimers formed between monomers emanating from opposing cell surfaces. Lateral cis interfaces between cadherins from the same cell surface have been proposed to play a role in cadherin clustering. Although the molecular details of cis interactions remain uncertain, they must define an anisotropic arrangement where binding is favorable only in certain orientations. Here we report Monte Carlo simulations performed on a 2D lattice constructed to account for the anisotropy in cadherin cis interactions. A crucial finding is that the phase transition between freely diffusing cadherin monomers and dimers and a condensed ordered 2D junction formed by dimers alone is a cooperative process involving both trans and cis interactions. Moreover, cis interactions, despite being too weak to be measured in solution, are critical to the formation of an ordered junction structure. We discuss these results in light of available experimental information on cadherin binding free energies that are transformed from their bulk solution values to interaction energies on a 2D lattice.
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