Dimer conformation of soluble PECAM-1, an endothelial marker.
Platelet endothelial cell adhesion molecule 1 (PECAM-1) is a cell surface receptor widely distributed on endothelium and hematopoietic-derived cells, and maintain the integrity of the blood vessels. PECAM-1 is widely recognized as an endothelial cell marker. The homophilic interaction through its extracellular domain of PECAM-1 (soluble PECAM-1, or sPECAM-1) is important to its functions. However, structural details for such dimerization are not fully understood. Here we report the production of recombinant sPECAM-1 in large quantity by Drosophila expression system and the small-angle X-ray diffraction (SAXS) study. The recombinant sPECAM-1 was found to form one population of dimer, but not oligomer, and was able to bind to heparin immobilized on a chip in surface plasmon resonance imaging (SPRi) binding experiments. The results of SAXS demonstrated that sPECAM-1 formed a symmetric homodimer of Ω-shape in solution, and each protomer adopted an extended conformation. The dimer is mediated through the intermolecular interactions through the first N-terminal domain (D1) of sPECAM-1. This model provides new structural information for its homophilic interaction mechanism.
College of Chemistry, Fuzhou University, Fuzhou 350116, China; State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China.
Longguang
L
Jiang
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Lin
L
Lin
Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, China.
Rui
R
Li
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China.
Cai
C
Yuan
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China.
Mingming
M
Xu
Shanghai Medical college, Fudan University, Shanghai 200032, China.
Joy H
JH
Huang
College of Chemistry, Fuzhou University, Fuzhou 350116, China; State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China. Electronic address: mhuang@fjirsm.ac.cn.
Mingdong
M
Huang
D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D004727:Endothelium / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005786:Gene Expression Regulation; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D012995:Solubility
D015415:Biomarkers; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D006493:Heparin
Dimer; Homophilic interactions; Immunoglobulin domains; PECAM-1; SAXS