2J8J
Solution Structure of the A4 Domain of Blood Coagulation Factor XI
Summary for 2J8J
| Entry DOI | 10.2210/pdb2j8j/pdb |
| Related | 1XX9 1XXD 1XXF 1ZHM 1ZHP 1ZHR 1ZJD 1ZLR 1ZMJ 1ZML 1ZMN 1ZOM 1ZPZ 1ZRK 1ZSJ 1ZSK 1ZSL 1ZTJ 1ZTK 1ZTL 2J8L |
| Descriptor | COAGULATION FACTOR XI (1 entity in total) |
| Functional Keywords | protease, hydrolase, glycoprotein, polymorphism, serine protease, heparin-binding, disease mutation, fxi / blood coagulation / pan domain /apple domain / blood coagulation, alternative splicing |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Secreted: P03951 |
| Total number of polymer chains | 2 |
| Total formula weight | 19916.55 |
| Authors | Samuel, D.,Cheng, H.,Riley, P.W.,Canutescu, A.A.,Bu, Z.,Walsh, P.N.,Roder, H. (deposition date: 2006-10-25, release date: 2007-10-02, Last modification date: 2024-11-13) |
| Primary citation | Samuel, D.,Cheng, H.,Riley, P.W.,Canutescu, A.A.,Nagaswami, C.,Weisel, J.W.,Bu, Z.,Walsh, P.N.,Roder, H. Solution Structure of the A4 Domain of Factor Xi Sheds Light on the Mechanism of Zymogen Activation. Proc.Natl.Acad.Sci.USA, 104:15693-, 2007 Cited by PubMed Abstract: Factor XI (FXI) is a homodimeric blood coagulation protein. Each monomer comprises four tandem apple-domain repeats (A1-A4) and a serine protease domain. We report here the NMR solution structure of the A4 domain (residues 272-361), which mediates formation of the disulfide-linked FXI dimer. A4 exhibits characteristic features of the plasminogen apple nematode domain family, including a five-stranded beta-sheet flanked by an alpha-helix on one side and a two-stranded beta-sheet on the other. In addition, the solution structure reveals a second alpha-helix at the C terminus. Comparison with a recent crystal structure of full-length FXI, combined with molecular modeling, suggests that the C-terminal helix is formed only upon proteolytic activation. The newly formed helix disrupts interdomain contacts and reorients the catalytic domains, bringing the active sites into close proximity. This hypothesis is supported by small-angle x-ray scattering and electron microscopy data, which indicate that FXI activation is accompanied by a major change in shape. The results are consistent with biochemical evidence that activated FXI cleaves its substrate at two positions without release of an intermediate. PubMed: 17884987DOI: 10.1073/PNAS.0703080104 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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