PDBsum entry 2eh8

Immune system

PDB id: 2eh8

Contents

Protein chains

218 a.a. *

218 a.a. *

Ligands

ALA-ASN-SER-ASN-ASN-PRO-ASP-TRP-ASP-PHE

Waters ×41

* Residue conservation analysis

PDB id:

2eh8

Name:

Immune system

Title:

Crystal structure of the complex of humanized kr127 fab and pres1 peptide epitope

Structure:

Humanized kr127 fab, light chain. Chain: l. Engineered: yes. Humanized kr127 fab, heavy chain. Chain: h. Engineered: yes. Pres1/pres2/surface protein. Chain: p. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: humanized kr127. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: dg44. Expression_system_cell: dhfr-deficient cho cell. Synthetic: yes.

Resolution:

2.60Å R-factor: 0.193 R-free: 0.258

Authors:

S.-W.Chi,S.-J.Kim,C.-Y.Maeng,H.J.Hong,S.-E.Ryu

Key ref:

S.W.Chi et al. (2007). Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism. Proc Natl Acad Sci U S A, 104, 9230-9235. PubMed id: 17517649 DOI: 10.1073/pnas.0701279104

Date:

05-Mar-07 Release date: 15-Jan-08

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

DOI no: 10.1073/pnas.0701279104

Proc Natl Acad Sci U S A 104:9230-9235 (2007)

PubMed id: 17517649

Broadly neutralizing anti-hepatitis B virus antibody reveals a complementarity determining region H3 lid-opening mechanism.

S.W.Chi, C.Y.Maeng, S.J.Kim, M.S.Oh, C.J.Ryu, S.J.Kim, K.H.Han, H.J.Hong, S.E.Ryu.

ABSTRACT

The humanized monoclonal antibody HzKR127 recognizes the preS1 domain of the human hepatitis B virus surface proteins with a broadly neutralizing activity in vivo. We present the crystal structures of HzKR127 Fab and its complex with a major epitope peptide. In the complex structure, the bound peptide forms a type IV beta-turn followed by 3(10) helical turn, the looped-out conformation of which provides a structural basis for broad neutralization. Upon peptide binding, the antibody undergoes a dramatic complementarity determining region H3 lid opening. To understand the structural implication of the virus neutralization, we carried out comprehensive alanine-scanning mutagenesis of all complementarity determining region residues in HzKR127 Fab. The functional mapping of the antigen-combining site demonstrates the specific roles of major binding determinants in antigen binding, contributing to the rational design for maximal humanization and affinity maturation of the antibody.

Selected figure(s)

Figure 1.
Fig. 1. Domains of HBV surface proteins. The domain structures of S, M, and L proteins are presented with each domain colored differently. The adr subtype preS1 includes an epitope that is recognized by the neutralizing monoclonal antibody HzKR127. The peptide sequence of the epitope region is presented below the preS1 domain, with the epitope colored red.

Figure 3.
Fig. 3. Comparison of antigen-binding site in the free and bound HzKR127 Fabs. Interactions between the H3 lid (yellow) and neighbors in the free (Left) and bound (Right) HzKR127 Fabs. The residues involved in the interactions are drawn, and the major interactions are presented as dotted lines. The light and heavy chains are colored pink and blue (labeled red and blue), respectively. The bound peptide residues Pro6P–Trp8P are presented as sticks with atomic colors.

Figures were selected by an automated process.