Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Schwarzenbacher, R; Zeth, K; Diederichs, K; Gries, A; Kostner, GM; Laggner, P; Prassl, R.
Crystal structure of human beta2-glycoprotein I: implications for phospholipid binding and the antiphospholipid syndrome.
EMBO J. 1999; 18(22):6228-6239
Doi: 10.1093/emboj/18.22.6228
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- Führende Autor*innen der Med Uni Graz
- Prassl Ruth
- Co-Autor*innen der Med Uni Graz
- Gries Anna
- Kostner Gerhard
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Animals -
- Apolipoproteins - chemistry
- Binding Sites - chemistry
- Computer Graphics - chemistry
- Crystallography, X-Ray - chemistry
- Drosophila - chemistry
- Glycoproteins - chemistry
- Humans - chemistry
- Models, Molecular - chemistry
- Molecular Sequence Data - chemistry
- Protein Structure, Secondary - chemistry
- Sequence Alignment - chemistry
- Sequence Homology, Amino Acid - chemistry
- beta 2-Glycoprotein I - chemistry
- Find related publications in this database (Keywords)
- Apolipoprotein H (Apoh)
- Complement Control Protein
- Beta-2-Glycoprotein I
- Short Consensus Repeat
- Sushi Domain