PDBsum entry: 2fib

Complex (blood coagulation/peptide)

PDB id: 2fib

Contents

Protein chain

250 a.a. *

Ligands

GLY-PRO-ARG-PRO

Metals

_CA

Waters ×115

* Residue conservation analysis

PDB id:

2fib

Name:

Complex (blood coagulation/peptide)

Title:

Recombinant human gamma-fibrinogen carboxyl terminal fragment (residues 143-411) complexed to the peptide gly- pro-arg-pro at ph 6.0

Structure:

Fibrinogen. Chain: a. Fragment: gamma chain, carboxyl terminal fragment residues 143 - 411. Engineered: yes. Gly-pro-arg-pro. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Organ: blood. Tissue: blood plasma. Gene: human fibrinogen gamma chain cdna encoding val 143 - val 411. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Biol. unit:

Dimer (from PQS)

Resolution:

2.01Å R-factor: 0.186 R-free: 0.282

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

Date:

03-Jun-97 Release date: 15-Oct-97

Protein chain

P02679  (FIBG_HUMAN) -  Fibrinogen gamma chain

Seq: 453 a.a.

Struc: 250 a.a.

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular space (1 term)
• Biological process: signal transduction (1 term)
• Biochemical function: receptor binding (1 term)

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.

ABSTRACT

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.