Structural basis for human PECAM-1-mediated trans-homophilic cell adhesion
Abstract
Cell adhesion involved in signal transduction, tissue integrity and pathogen infection is mainly mediated by cell adhesion molecules (CAM). One CAM member, platelet–endothelial-cell adhesion molecule-1 (PECAM-1), plays an important role in tight junction among endothelia cells, leukocyte trafficking, and immune response through its homophilic and heterophilic binding patterns. Both kinds of interactions, which lead to endogenous and exogenous signal transmission, are derived from extracellular immunoglobulin-like (IgL) domains and cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of PECAM-1. To date, the mechanism of trans-homophilic interaction of PECAM-1 remains unclear. Here, we present the crystal structure of PECAM-1 IgL1-2 trans-homo dimer. Both IgL 1 and 2 adopt the classical Ig domain conformation comprised of two layers of β-sheets possessing antiparallel β-strands with each being anchored by a pair of cysteines forming a disulfide bond. The dimer interface includes hydrophobic and hydrophilic interactions. The Small-Angle X-ray Scattering (SAXS) envelope of PECAM-1 IgL1-6 supported such a dimer formation in solution. As a result, cell adhesion assays on wildtype and mutant PECAM-1 further characterized the structural determinants in cell junction and communication.
- Authors:
-
- Univ. of Hong Kong, Hong Kong (China)
- Southern Univ. of Science and Technology, Shenzhen (China)
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Publication Date:
- Research Org.:
- Brookhaven National Laboratory (BNL), Upton, NY (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER)
- OSTI Identifier:
- 1347367
- Report Number(s):
- BNL-113639-2017-JA
Journal ID: ISSN 2045-2322
- Grant/Contract Number:
- SC00112704
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Scientific Reports
- Additional Journal Information:
- Journal Volume: 6; Journal Issue: 1; Journal ID: ISSN 2045-2322
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; PECAM-1; CD31; trans-homophilic dimer; cell adhesion; X-ray; crystallography
Citation Formats
Hu, Menglong, Zhang, Hongmin, Liu, Qun, and Hao, Quan. Structural basis for human PECAM-1-mediated trans-homophilic cell adhesion. United States: N. p., 2016.
Web. doi:10.1038/srep38655.
Hu, Menglong, Zhang, Hongmin, Liu, Qun, & Hao, Quan. Structural basis for human PECAM-1-mediated trans-homophilic cell adhesion. United States. https://doi.org/10.1038/srep38655
Hu, Menglong, Zhang, Hongmin, Liu, Qun, and Hao, Quan. Tue .
"Structural basis for human PECAM-1-mediated trans-homophilic cell adhesion". United States. https://doi.org/10.1038/srep38655. https://www.osti.gov/servlets/purl/1347367.
@article{osti_1347367,
title = {Structural basis for human PECAM-1-mediated trans-homophilic cell adhesion},
author = {Hu, Menglong and Zhang, Hongmin and Liu, Qun and Hao, Quan},
abstractNote = {Cell adhesion involved in signal transduction, tissue integrity and pathogen infection is mainly mediated by cell adhesion molecules (CAM). One CAM member, platelet–endothelial-cell adhesion molecule-1 (PECAM-1), plays an important role in tight junction among endothelia cells, leukocyte trafficking, and immune response through its homophilic and heterophilic binding patterns. Both kinds of interactions, which lead to endogenous and exogenous signal transmission, are derived from extracellular immunoglobulin-like (IgL) domains and cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of PECAM-1. To date, the mechanism of trans-homophilic interaction of PECAM-1 remains unclear. Here, we present the crystal structure of PECAM-1 IgL1-2 trans-homo dimer. Both IgL 1 and 2 adopt the classical Ig domain conformation comprised of two layers of β-sheets possessing antiparallel β-strands with each being anchored by a pair of cysteines forming a disulfide bond. The dimer interface includes hydrophobic and hydrophilic interactions. The Small-Angle X-ray Scattering (SAXS) envelope of PECAM-1 IgL1-6 supported such a dimer formation in solution. As a result, cell adhesion assays on wildtype and mutant PECAM-1 further characterized the structural determinants in cell junction and communication.},
doi = {10.1038/srep38655},
journal = {Scientific Reports},
number = 1,
volume = 6,
place = {United States},
year = {Tue Dec 13 00:00:00 EST 2016},
month = {Tue Dec 13 00:00:00 EST 2016}
}
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