PDBsum entry 3bvh

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protein ligands metals Protein-protein interface(s) links
Blood clotting PDB id
Protein chains
62 a.a. *
298 a.a. *
293 a.a. *
_CA ×4
Waters ×446
* Residue conservation analysis
PDB id:
Name: Blood clotting
Title: Crystal structure of recombinant gammad364a fibrinogen fragm the peptide ligand gly-pro-arg-pro-amide
Structure: Fibrinogen alpha chain. Chain: a, d. Fragment: residues 148-209. Engineered: yes. Fibrinogen beta chain. Chain: b, e. Fragment: residues 191-488. Engineered: yes. Fibrinogen gamma chain.
Source: Homo sapiens. Human. Gene: fga. Expressed in: cricetulus griseus. Gene: fgb. Gene: fgg. Synthetic: yes. Other_details: synthetic peptide
2.60Å     R-factor:   0.220     R-free:   0.260
Authors: S.R.Bowley,B.K.Merenbloom,L.Betts,N.Okumura,A.Heroux,O.V.Gor S.T.Lord
Key ref: S.R.Bowley et al. (2008). Polymerization-defective fibrinogen variant gammaD364A binds knob "A" peptide mimic. Biochemistry, 47, 8607-8613. PubMed id: 18642883 DOI: 10.1021/bi8000769
07-Jan-08     Release date:   02-Sep-08    
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Protein chains
Pfam   ArchSchema ?
P02671  (FIBA_HUMAN) -  Fibrinogen alpha chain
866 a.a.
62 a.a.
Protein chains
Pfam   ArchSchema ?
P02675  (FIBB_HUMAN) -  Fibrinogen beta chain
491 a.a.
298 a.a.
Protein chains
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
453 a.a.
293 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     fibrinogen complex   1 term 
  Biological process     signal transduction   3 terms 
  Biochemical function     receptor binding     2 terms  


DOI no: 10.1021/bi8000769 Biochemistry 47:8607-8613 (2008)
PubMed id: 18642883  
Polymerization-defective fibrinogen variant gammaD364A binds knob "A" peptide mimic.
S.R.Bowley, B.K.Merenbloom, N.Okumura, L.Betts, A.Heroux, O.V.Gorkun, S.T.Lord.
Fibrin polymerization is supported in part by interactions called "A:a". Crystallographic studies revealed gamma364Asp is part of hole "a" that interacts with knob "A" peptide mimic, GPRP. Biochemical studies have shown gamma364Asp is critical to polymerization, as polymerization of variants gammaD364A, gammaD364H, and gammaD364V is exceptionally impaired. To understand the molecular basis for the aberrant function, we solved the crystal structure of fragment D from gammaD364A. Surprisingly, the structure (rfD-gammaD364A+GP) showed near normal "A:a" interactions with GPRP bound to hole "a" and no change in the overall structure of gammaD364A. Of note, inspection of the structure showed negative electrostatic potential inside hole "a" was diminished by this substitution. We examined GPRP binding to the gamma364Asp variants in solution by plasmin protection assay. We found no protection of either gammaD364H or gammaD364V but partial protection of gammaD364A, indicating the peptide does not bind to either gammaD364H or gammaD364V and binds more weakly than normal to gammaD364A. We also examined protection by calcium and found all variants were indistinguishable from normal, suggesting the global structures of the variants are not markedly different from normal. Our data imply that gamma364Asp per se is not required for knob "A" binding to hole "a"; rather, this residue's negative charge has a critical role in the electrostatic interactions that facilitate the important first step in fibrin polymerization.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20484082 S.E.Stabenfeldt, J.J.Gossett, and T.H.Barker (2010).
Building better fibrin knob mimics: an investigation of synthetic fibrin knob peptide structures in solution and their dynamic binding with fibrinogen/fibrin holes.
  Blood, 116, 1352-1359.  
19650644 S.R.Bowley, N.Okumura, and S.T.Lord (2009).
Impaired protofibril formation in fibrinogen gamma N308K is due to altered D:D and "A:a" interactions.
  Biochemistry, 48, 8656-8663.
PDB code: 3hus
19075185 S.R.Bowley, and S.T.Lord (2009).
Fibrinogen variant BbetaD432A has normal polymerization but does not bind knob "B".
  Blood, 113, 4425-4430.
PDB code: 3e1i
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