PDBsum entry 1p2c

Immune system/hydrolase

PDB id: 1p2c

Contents

Protein chains

212 a.a. *

210 a.a. *

129 a.a. *

Waters ×887

* Residue conservation analysis

PDB id:

1p2c

Name:

Immune system/hydrolase

Title:

Crystal structure analysis of an anti-lysozyme antibody

Structure:

Light chain anti-lysozyme antibody f10.6.6. Chain: a, d. Heavy chain vh+ch1 anti-lysozyme antibody f10.6.6. Chain: b, e. LysozymE C. Chain: c, f. Synonym: 1,4-beta-n-acetylmuramidasE C, allergen gal d 4, gal d iv. Ec: 3.2.1.17

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb-c. Gallus gallus. Chicken. Organism_taxid: 9031

Biol. unit:

Trimer (from PQS)

Resolution:

2.00Å R-factor: 0.204 R-free: 0.242

Authors:

A.Cauerhff,F.A.Goldbaum,B.C.Braden

Key ref:

A.Cauerhff et al. (2004). Structural mechanism for affinity maturation of an anti-lysozyme antibody. Proc Natl Acad Sci U S A, 101, 3539-3544. PubMed id: 14988501 DOI: 10.1073/pnas.0400060101

Date:

15-Apr-03 Release date: 17-Feb-04

Protein chains

P01837  (IGKC_MOUSE) -  Immunoglobulin kappa constant from Mus musculus

Seq: 107 a.a.

Struc: 212 a.a.

Protein chains

P01868  (IGHG1_MOUSE) -  Ig gamma-1 chain C region secreted form from Mus musculus

Seq: 324 a.a.

Struc: 210 a.a.*

Protein chains

P00698  (LYSC_CHICK) -  Lysozyme C from Gallus gallus

Seq: 147 a.a.

Struc: 129 a.a.

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains C, F: E.C.3.2.1.17 - lysozyme.
• Reaction: Hydrolysis of the 1,4-beta-linkages between N-acetyl-D-glucosamine and N-acetylmuramic acid in peptidoglycan heteropolymers of the prokaryotes cell walls.

DOI no: 10.1073/pnas.0400060101

Proc Natl Acad Sci U S A 101:3539-3544 (2004)

PubMed id: 14988501

Structural mechanism for affinity maturation of an anti-lysozyme antibody.

A.Cauerhff, F.A.Goldbaum, B.C.Braden.

ABSTRACT

In the immune response against a typical T cell-dependent protein antigen, the affinity maturation process is fast and is associated with the early class switch from IgM to IgG. As such, a comprehension of the molecular basis of affinity maturation could be of great importance in biomedical and biotechnological applications. Affinity maturation of anti-protein antibodies has been reported to be the result of small structural changes, mostly confined to the periphery of the antigen-combining site. However, little is understood about how these small structural changes account for the increase in the affinity toward the antigen. Herein, we present the three-dimensional structure of the Fab fragment from BALB/c mouse mAb F10.6.6 in complex with the antigen lysozyme. This antibody was obtained from a long-term exposure to the antigen. mAb F10.6.6, and the previously described antibody D44.1, are the result of identical or nearly identical somatic recombination events. However, different mutations in the framework and variable regions result in an approximately 10(3) higher affinity for the F10.6.6 antibody. The comparison of the three-dimensional structures of these Fab-lysozyme complexes reveals that the affinity maturation produces a fine tuning of the complementarity of the antigen-combining site toward the epitope, explaining at the molecular level how the immune system is able to increase the affinity of an anti-protein antibody to subnanomolar levels.

Selected figure(s)

Figure 2.
Fig. 2. Superposition of F10.6.6-HEL (yellow) and D44.1-HEL (light blue). For clarity, the F[V]-HEL of only one F10.6.6-HEL and one D44.1-HEL is shown. The superposition identifies no remarkable conformational differences between F10.6.6 and D44.1; however, the HEL in the D44.1 complex shows a displacement away from the antibody, as compared with the F10.6.6-HEL structure.

Figure 3.
Fig. 3. Stereoview of the CDR L3/HEL interaction in F10.6.6/HEL (yellow) and D44.1/HEL (light blue) complexes. The dislocation of the HEL carbonyl by D44.1 CDRL3 Asn is evident. The average displacement of the HEL C s in the D44.1-HEL structures is 0.45 Å.

Figures were selected by an automated process.