PDBsum entry 3fib

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protein metals links
Blood coagulation PDB id
Protein chain
249 a.a. *
Waters ×177
* Residue conservation analysis
PDB id:
Name: Blood coagulation
Title: Recombinant human gamma-fibrinogen carboxyl terminal fragment (residues 143-411) bound to calcium at ph 6.0: a further refinement of PDB entry 1fib, and differs from 1fib by the modelling of a cis peptide bond between residues k338 and c339
Structure: Fibrinogen gamma chain residues. Chain: a. Fragment: residues 143 - 411. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: blood. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
2.10Å     R-factor:   0.154     R-free:   0.206
Authors: K.P.Pratt,H.C.F.Cote,D.W.Chung,R.E.Stenkamp,E.W.Davie
Key ref:
K.P.Pratt et al. (1997). The primary fibrin polymerization pocket: three-dimensional structure of a 30-kDa C-terminal gamma chain fragment complexed with the peptide Gly-Pro-Arg-Pro. Proc Natl Acad Sci U S A, 94, 7176-7181. PubMed id: 9207064 DOI: 10.1073/pnas.94.14.7176
14-Jul-97     Release date:   17-Sep-97    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain
453 a.a.
249 a.a.
Key:    PfamA domain  Secondary structure  CATH domain


DOI no: 10.1073/pnas.94.14.7176 Proc Natl Acad Sci U S A 94:7176-7181 (1997)
PubMed id: 9207064  
The primary fibrin polymerization pocket: three-dimensional structure of a 30-kDa C-terminal gamma chain fragment complexed with the peptide Gly-Pro-Arg-Pro.
K.P.Pratt, H.C.Côté, D.W.Chung, R.E.Stenkamp, E.W.Davie.
After vascular injury, a cascade of serine protease activations leads to the conversion of the soluble fibrinogen molecule into fibrin. The fibrin monomers then polymerize spontaneously and noncovalently to form a fibrin gel. The primary interaction of this polymerization reaction is between the newly exposed N-terminal Gly-Pro-Arg sequence of the alpha chain of one fibrin molecule and the C-terminal region of a gamma chain of an adjacent fibrin(ogen) molecule. In this report, the polymerization pocket has been identified by determining the crystal structure of a 30-kDa C-terminal fragment of the fibrin(ogen) gamma chain complexed with the peptide Gly-Pro-Arg-Pro. This peptide mimics the N terminus of the alpha chain of fibrin. The conformational change in the protein upon binding the peptide is subtle, with electrostatic interactions primarily mediating the association. This is consistent with biophysical experiments carried out over the last 50 years on this fundamental polymerization reaction.
  Selected figure(s)  
Figure 1.
Fig. 1. Simplified model of interactions between adjacent fibrin chains at the beginning of the polymerization reaction. Thrombin cleaves the chain N terminus, creating a new N terminus (the^ A site) beginning with the sequence Gly-Pro-Arg. The A site binds to the complementary "a" polymerization pocket in the chain during the alignment of the fibrin protofibrils.
Figure 3.
Fig. 3. Schematic of interactions between GPRP and the protein. Hydrogen bonds and favorable ionic interactions are indicated by dotted^ lines. One of the terminal nitrogens of the arginine side chain is 3.26 Å away from the carbonyl oxygen of the first peptide proline, creating a weak hydrogen bond.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21382527 E.Akpalo, L.Bidault, M.Boissière, C.Vancaeyzeele, O.Fichet, and V.L.Garde (2011).
Fibrin-polyethylene oxide interpenetrating polymer networks: New self-supported biomaterials combining the properties of both protein gel and synthetic polymer.
  Acta Biomater, 7, 2418-2427.  
20981788 J.Y.Chen, W.N.Chen, L.L.Liu, W.S.Lin, B.Y.Jiao, Y.L.Wu, J.Y.Lin, and X.Lin (2010).
Hepatitis B spliced protein (HBSP) generated by a spliced hepatitis B virus RNA participates in abnormality of fibrin formation and functions by binding to fibrinogen γ chain.
  J Med Virol, 82, 2019-2026.  
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
19052234 E.T.O'Brien, M.R.Falvo, D.Millard, B.Eastwood, R.M.Taylor, and R.Superfine (2008).
Ultrathin self-assembled fibrin sheets.
  Proc Natl Acad Sci U S A, 105, 19438-19443.  
18421149 M.Tanio, S.Kondo, S.Sugio, and T.Kohno (2008).
Trimeric structure and conformational equilibrium of M-ficolin fibrinogen-like domain.
  J Synchrotron Radiat, 15, 243-245.  
18710925 T.A.Springer, J.Zhu, and T.Xiao (2008).
Structural basis for distinctive recognition of fibrinogen gammaC peptide by the platelet integrin alphaIIbbeta3.
  J Cell Biol, 182, 791-800.
PDB codes: 2vc2 2vdk 2vdl 2vdm 2vdn 2vdo 2vdp 2vdq 2vdr
17892530 C.B.Geer, A.Tripathy, M.H.Schoenfisch, S.T.Lord, and O.V.Gorkun (2007).
Role of 'B-b' knob-hole interactions in fibrin binding to adsorbed fibrinogen.
  J Thromb Haemost, 5, 2344-2351.  
17883696 N.Dib, F.Quelin, C.Ternisien, M.Hanss, S.Michalak, P.De Mazancourt, M.C.Rousselet, and P.Calès (2007).
Fibrinogen angers with a new deletion (gamma GVYYQ 346-350) causes hypofibrinogenemia with hepatic storage.
  J Thromb Haemost, 5, 1999-2005.  
17922804 N.Okumura, F.Terasawa, A.Haneishi, N.Fujihara, M.Hirota-Kawadobora, K.Yamauchi, H.Ota, and S.T.Lord (2007).
B:b interactions are essential for polymerization of variant fibrinogens with impaired holes 'a'.
  J Thromb Haemost, 5, 2352-2359.  
  16820685 M.Tanio, S.Kondo, S.Sugio, and T.Kohno (2006).
Overexpression, purification and preliminary crystallographic analysis of human M-ficolin fibrinogen-like domain.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 62, 652-655.  
16999847 R.Asselta, S.Duga, and M.L.Tenchini (2006).
The molecular basis of quantitative fibrinogen disorders.
  J Thromb Haemost, 4, 2115-2129.  
16879216 T.Sugo, H.Endo, M.Matsuda, T.Ohmori, S.Madoiwa, J.Mimuro, and Y.Sakata (2006).
A classification of the fibrin network structures formed from the hereditary dysfibrinogens.
  J Thromb Haemost, 4, 1738-1746.  
16732286 W.A.Barton, D.Tzvetkova-Robev, E.P.Miranda, M.V.Kolev, K.R.Rajashankar, J.P.Himanen, and D.B.Nikolov (2006).
Crystal structures of the Tie2 receptor ectodomain and the angiopoietin-2-Tie2 complex.
  Nat Struct Mol Biol, 13, 524-532.
PDB codes: 2gy5 2gy7
16102057 M.W.Mosesson (2005).
Fibrinogen and fibrin structure and functions.
  J Thromb Haemost, 3, 1894-1904.  
15998829 R.I.Litvinov, O.V.Gorkun, S.F.Owen, H.Shuman, and J.W.Weisel (2005).
Polymerization of fibrin: specificity, strength, and stability of knob-hole interactions studied at the single-molecule level.
  Blood, 106, 2944-2951.  
15893672 W.A.Barton, D.Tzvetkova, and D.B.Nikolov (2005).
Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition.
  Structure, 13, 825-832.
PDB codes: 1z3s 1z3u
15099268 R.F.Doolittle (2004).
Determining the crystal structure of fibrinogen.
  J Thromb Haemost, 2, 683-689.  
12695754 F.Mathonnet, L.Guillon, H.Detruit, G.M.Mazmanian, M.Dreyfus, J.C.Alvarez, Y.Giudicelli, and Mazancourt (2003).
Fibrinogen Poissy II (gammaN361K): a novel dysfibrinogenemia associated with defective polymerization and peptide B release.
  Blood Coagul Fibrinolysis, 14, 293-298.  
12871501 M.Hirota-Kawadobora, F.Terasawa, O.Yonekawa, N.Sahara, E.Shimizu, N.Okumura, T.Katsuyama, and H.Shigematsu (2003).
Fibrinogens Kosai and Ogasa: Bbeta15Gly-->Cys (GGT-->TGT) substitution associated with impairment of fibrinopeptide B release and lateral aggregation.
  J Thromb Haemost, 1, 275-283.  
12871494 M.W.Mosesson (2003).
Fibrinogen gamma chain functions.
  J Thromb Haemost, 1, 231-238.  
12871291 R.F.Doolittle (2003).
X-ray crystallographic studies on fibrinogen and fibrin.
  J Thromb Haemost, 1, 1559-1565.  
12490209 R.F.Doolittle (2003).
Structural basis of the fibrinogen-fibrin transformation: contributions from X-ray crystallography.
  Blood Rev, 17, 33-41.  
12485987 C.C.Deivanayagam, E.R.Wann, W.Chen, M.Carson, K.R.Rajashankar, M.Höök, and S.V.Narayana (2002).
A novel variant of the immunoglobulin fold in surface adhesins of Staphylococcus aureus: crystal structure of the fibrinogen-binding MSCRAMM, clumping factor A.
  EMBO J, 21, 6660-6672.
PDB code: 1n67
  12617173 S.J.Everse (2002).
New insights into fibrin (ogen) structure and function.
  Vox Sang, 83, 375-382.  
11707569 N.Kairies, H.G.Beisel, P.Fuentes-Prior, R.Tsuda, T.Muta, S.Iwanaga, W.Bode, R.Huber, and S.Kawabata (2001).
The 2.0-A crystal structure of tachylectin 5A provides evidence for the common origin of the innate immunity and the blood coagulation systems.
  Proc Natl Acad Sci U S A, 98, 13519-13524.
PDB code: 1jc9
10618375 J.H.Brown, N.Volkmann, G.Jun, A.H.Henschen-Edman, and C.Cohen (2000).
The crystal structure of modified bovine fibrinogen.
  Proc Natl Acad Sci U S A, 97, 85-90.
PDB code: 1deq
11123898 S.Yakovlev, E.Makogonenko, N.Kurochkina, W.Nieuwenhuizen, K.Ingham, and L.Medved (2000).
Conversion of fibrinogen to fibrin: mechanism of exposure of tPA- and plasminogen-binding sites.
  Biochemistry, 39, 15730-15741.  
11123897 S.Yakovlev, S.Litvinovich, D.Loukinov, and L.Medved (2000).
Role of the beta-strand insert in the central domain of the fibrinogen gamma-module.
  Biochemistry, 39, 15721-15729.  
11121023 Z.Yang, I.Mochalkin, and R.F.Doolittle (2000).
A model of fibrin formation based on crystal structures of fibrinogen and fibrin fragments complexed with synthetic peptides.
  Proc Natl Acad Sci U S A, 97, 14156-14161.  
10479736 M.S.Weiss, and R.Hilgenfeld (1999).
A method to detect nonproline cis peptide bonds in proteins.
  Biopolymers, 50, 536-544.  
10074346 S.J.Everse, G.Spraggon, L.Veerapandian, and R.F.Doolittle (1999).
Conformational changes in fragments D and double-D from human fibrin(ogen) upon binding the peptide ligand Gly-His-Arg-Pro-amide.
  Biochemistry, 38, 2941-2946.
PDB codes: 1fze 1fzf 1fzg
  9755198 E.C.Lee, S.Y.Yu, X.Hu, M.Mlodzik, and N.E.Baker (1998).
Functional analysis of the fibrinogen-related scabrous gene from Drosophila melanogaster identifies potential effector and stimulatory protein domains.
  Genetics, 150, 663-673.  
9689040 G.Spraggon, D.Applegate, S.J.Everse, J.Z.Zhang, L.Veerapandian, C.Redman, R.F.Doolittle, and G.Grieninger (1998).
Crystal structure of a recombinant alphaEC domain from human fibrinogen-420.
  Proc Natl Acad Sci U S A, 95, 9099-9104.
PDB code: 1fzd
9435227 L.Lorand, K.N.Parameswaran, and S.N.Murthy (1998).
A double-headed Gly-Pro-Arg-Pro ligand mimics the functions of the E domain of fibrin for promoting the end-to-end crosslinking of gamma chains by factor XIIIa.
  Proc Natl Acad Sci U S A, 95, 537-541.  
9920398 Q.Liu, and M.M.Frojmovic (1998).
The fibrinogen RIBS-I epitope (gamma373-385) appears proximate to the gamma408-411 adhesive domain but is not involved in interaction between receptor-bound or surface-adsorbed fibrinogen and platelet GPIIbIIIa.
  Biochim Biophys Acta, 1429, 217-229.  
9914253 R.F.Doolittle, G.Spraggon, and S.J.Everse (1998).
Three-dimensional structural studies on fragments of fibrinogen and fibrin.
  Curr Opin Struct Biol, 8, 792-798.  
9628725 S.J.Everse, G.Spraggon, L.Veerapandian, M.Riley, and R.F.Doolittle (1998).
Crystal structure of fragment double-D from human fibrin with two different bound ligands.
  Biochemistry, 37, 8637-8642.
PDB code: 1fzc
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.