1CKL

N-TERMINAL TWO DOMAINS OF HUMAN CD46 (MEMBRANE COFACTOR PROTEIN, MCP)

Summary for 1CKL

• Entry DOI: 10.2210/pdb1ckl/pdb
• Descriptor: PROTEIN (CD46), CHLORIDE ION, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: virus receptor, complement cofactor, short consensus repeat, scr, measles virus, glycoprotein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasmic vesicle, secretory vesicle, acrosome inner membrane; Single-pass type I membrane protein: P15529
• Total number of polymer chains: 6
• Total formula weight: 96993.65

Authors

Casasnovas, J.,Larvie, M.,Stehle, T. (deposition date: 1999-04-22, release date: 1999-06-11, Last modification date: 2024-11-13)

Primary citation

Casasnovas, J.M.,Larvie, M.,Stehle, T.
Crystal structure of two CD46 domains reveals an extended measles virus-binding surface.
EMBO J., 18:2911-2922, 1999

PubMed Abstract: Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide. The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 A resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface. Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition. A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46.

PubMed: 10357804
DOI: 10.1093/emboj/18.11.2911

Experimental method

X-RAY DIFFRACTION (3.1 Å)