PDBsum entry 1n64

Immune system

PDB id: 1n64

Contents

Protein chains

220 a.a. *

218 a.a. *

16 a.a. *

Waters ×202

* Residue conservation analysis

PDB id:

1n64

Name:

Immune system

Title:

Crystal structure analysis of the immunodominant antigenic site on hepatitis c virus protein bound to mab 19d9d6

Structure:

Fab 19d9d6 light chain. Chain: l. Fab 19d9d6 heavy chain. Chain: h. Engineered: yes. Genome polyprotein capsid protein c. Chain: p. Synonym: hcv core 13-40 peptide, core protein, p22. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Synthetic: yes. Other_details: sequence from hepatitis c virus core protein

Biol. unit:

Trimer (from PQS)

Resolution:

2.34Å R-factor: 0.190 R-free: 0.245

Authors:

R.Menez,M.Bossus,B.Muller,G.Sibai,P.Dalbon,F.Ducancel,C.Jolivet- Reynaud,E.Stura

Key ref:

R.Ménez et al. (2003). Crystal structure of a hydrophobic immunodominant antigenic site on hepatitis C virus core protein complexed to monoclonal antibody 19D9D6. J Immunol, 170, 1917-1924. PubMed id: 12574359

Date:

08-Nov-02 Release date: 25-Feb-03

Protein chain

No UniProt id for this chain

Struc: 220 a.a.

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

Protein chain

P29846  (POLG_HCVTW) -  Genome polyprotein from Hepatitis C virus genotype 1b (isolate Taiwan)

Seq: 3010 a.a.

Struc: 16 a.a.

Enzyme reactions

• Enzyme class 1: Chain P: E.C.2.7.7.48 - RNA-directed Rna polymerase.
• Reaction: RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphate
• Enzyme class 2: Chain P: E.C.3.4.21.98 - hepacivirin.
• Reaction: Hydrolysis of four peptide bonds in the viral precursor polyprotein, commonly with Asp or Glu in the P6 position, Cys or Thr in P1 and Ser or Ala in P1'.
• Enzyme class 3: Chain P: E.C.3.4.22.- - ?????
• Enzyme class 4: Chain P: E.C.3.6.1.15 - nucleoside-triphosphate phosphatase.
• Reaction: a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H⁺
• Enzyme class 5: Chain P: E.C.3.6.4.13 - Rna helicase.
• Reaction: ATP + H2O = ADP + phosphate + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

J Immunol 170:1917-1924 (2003)

PubMed id: 12574359

Crystal structure of a hydrophobic immunodominant antigenic site on hepatitis C virus core protein complexed to monoclonal antibody 19D9D6.

R.Ménez, M.Bossus, B.H.Muller, G.Sibaï, P.Dalbon, F.Ducancel, C.Jolivet-Reynaud, E.A.Stura.

ABSTRACT

The first crystal structure of a complex between a hepatitis C virus (HCV) core protein-derived peptide (residues 13-40) and the Ab fragment of a murine mAb (19D9D6) has been solved, allowing determination of the recognized epitope and elucidation of its conformation. This Ab, raised against the first 120 residues of the core protein, recognizes core particles and strongly competes with anticore human Abs, suggesting that it is highly representative of the human anti-HCV core response. Its epitope lies within the first 45 aa of the protein, the major antigenic segment of core recognized both by murine and human Abs. Surprisingly, the recognized epitope (29-37: QIVGGVYLL) has an unusual preponderance of hydrophobic residues, some of which are buried in a small hydrophobic core in the nuclear magnetic resonance structure of the peptide (2-45) in solution, suggesting that the Ab may induce a structural rearrangement upon recognition. The flexibility may reside entirely within the Ag, since the Fab'-peptide complex structure at 2.34 A shows that the Ab binding site is hardly perturbed by complexation. Given that the recognized residues are unlikely to be solvent exposed, we are left with the interesting possibility that Ab-core interactions may take place in a nonaqueous environment.