title: 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. Cell adhesion assays on wildtype and mutant PECAM-1 further characterized the structural determinants in cell junction and communication.
authors.affiliation: School of Biomedical Sciences, University of Hong Kong, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China.
authors.forename: Menglong
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen 518055, China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Liu
authors.affiliation: School of Biomedical Sciences, University of Hong Kong, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
mesh_terms: D002448:Cell Adhesion; D002460:Cell Line; D004252:DNA Mutational Analysis; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D053838:Scattering, Small Angle; D012996:Solutions; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012996:Solutions