1C1Z

CRYSTAL STRUCTURE OF HUMAN BETA-2-GLYCOPROTEIN-I (APOLIPOPROTEIN-H)

Summary for 1C1Z

• Entry DOI: 10.2210/pdb1c1z/pdb
• Related: 1CKL 1HFH 1QUB 1VVC
• Descriptor: BETA2-GLYCOPROTEIN-I, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, beta-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: glycoprotein, short consensus repeat, scr, sushi domain, complement control protein module, ccp, signaling protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 38456.59

Authors

Schwarzenbacher, R.,Zeth, K.,Diederichs, K.,Gries, A.,Kostner, G.M.,Laggner, P.,Prassl, R. (deposition date: 1999-07-22, release date: 1999-11-19, Last modification date: 2024-10-30)

Primary citation

Schwarzenbacher, R.,Zeth, K.,Diederichs, K.,Gries, A.,Kostner, G.M.,Laggner, P.,Prassl, R.
Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome.
EMBO J., 18:6228-6239, 1999

PubMed Abstract: The high affinity of human plasma beta2-glycoprotein I (beta(2)GPI), also known as apolipoprotein-H (ApoH), for negatively charged phospholipids determines its implication in a variety of physiological pathways, including blood coagulation and the immune response. beta(2)GPI is considered to be a cofactor for the binding of serum autoantibodies from antiphospholipid syndrome (APS) and correlated with thrombosis, lupus erythematosus and recurrent fetal loss. We solved the beta(2)GPI structure from a crystal form with 84% solvent and present a model containing all 326 amino acid residues and four glycans. The structure reveals four complement control protein modules and a distinctly folding fifth C-terminal domain arranged like beads on a string to form an elongated J-shaped molecule. Domain V folds into a central beta-spiral of four antiparallel beta-sheets with two small helices and an extended C-terminal loop region. It carries a distinct positive charge and the sequence motif CKNKEKKC close to the hydrophobic loop composed of residues LAFW (313-316), resulting in an excellent counterpart for interactions with negatively charged amphiphilic substances. The beta(2)GPI structure reveals potential autoantibody-binding sites and supports mutagenesis studies where Trp316 and CKNKEKKC have been found to be essential for the phospholipid-binding capacity of beta(2)GPI.

PubMed: 10562535
DOI: 10.1093/emboj/18.22.6228

Experimental method

X-RAY DIFFRACTION (2.87 Å)