5i25

human recombinant coagulation FXI in complex with a peptide derived from human high molecular weight kininogen (HKP)

spinqualitylabelsall models 5i25, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5i25 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.85Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease FA11_HUMAN Defects in F11 are the cause of factor XI deficiency (FA11D) [MIM:612416; also known as plasma thromboplastin antecedent deficiency or Rosenthal syndrome. It is a hemorrhagic disease characterized by reduced levels and activity of factor XI resulting in moderate bleeding symptoms, usually occurring after trauma or surgery. Patients usually do not present spontaneous bleeding but women can present with menorrhagia. Hemorrhages are usually moderate. Function FA11_HUMAN Factor XI triggers the middle phase of the intrinsic pathway of blood coagulation by activating factor IX. Publication Abstract from PubMed Factor XI (FXI) is the zymogen of factor XIa (FXIa) which cleaves factor IX in the intrinsic pathway of coagulation. FXI is known to exist as a dimer and form interactions with multiple proteins via its four apple domains in the "saucer section" of the enzyme however to date, no complex crystal structure has been described. To investigate protein interactions of FXI a large random peptide library consisting of 106-107peptides was screened for FXI binding and this identified a series of FXI binding motifs containing the signature Asp-Phe-Pro (DFP) tripeptide. Motifs containing this core tripeptide were found in diverse proteins including the known ligand high molecular weight kininogen (HK) as well as extracellular matrix proteins laminin and collagen V. To define the binding site on FXI we determined the crystal structure of FXI in complex with the HK derived peptide NPISDFPDT. This revealed the location of the DFP peptide bound to the FXI apple 2 domain and central to the interaction the DFP phenylalanine side chain inserts into a major hydrophobic pocket in the apple 2 domain and the isoleucine occupies a flanking minor pocket. Two further structures of FXI in complex with the laminin derived peptide EFPDFPand a DFP peptide from the random screen demonstrated binding in the same pocket although in a slightly different conformation, thus revealing some flexibility in the molecular interactions of the FXI apple 2 domain. A novel DFP tripeptide motif interacts with the coagulation factor XI apple 2 domain.,Wong SS, Ostergaard S, Hall G, Li C, Williams PM, Stennicke H, Emsley J Blood. 2016 Mar 22. pii: blood-2015-10-676122. PMID:27006387 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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