PDBsum entry 1c12

Immune system

PDB id: 1c12

Contents

Protein chains

214 a.a. *

220 a.a. *

Ligands

TRZ

Waters ×114

* Residue conservation analysis

PDB id:

1c12

Name:

Immune system

Title:

Insight in odorant perception: the crystal structure and binding characteristics of antibody fragments directed against the musk odorant traseolide

Structure:

Protein (antibody fragment fab). Chain: a. Engineered: yes. Protein (antibody fragment fab). Chain: b. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Organism_taxid: 10090

Biol. unit:

Tetramer (from PQS)

Resolution:

2.60Å R-factor: 0.205 R-free: 0.270

Authors:

A.C.Langedijk,S.Spinelli,C.Anguille,P.Hermans,J.Nederlof,J.Butenandt, A.Honegger,C.Cambillau,A.Pluckthun

Key ref:

A.C.Langedijk et al. (1999). Insight into odorant perception: the crystal structure and binding characteristics of antibody fragments directed against the musk odorant traseolide. J Mol Biol, 292, 855-869. PubMed id: 10525411 DOI: 10.1006/jmbi.1999.3101

Date:

20-Jul-99 Release date: 14-Aug-99

Protein chain

P01837  (IGKC_MOUSE) -  Immunoglobulin kappa constant from Mus musculus

Seq: 107 a.a.

Struc: 214 a.a.*

Protein chain

P01869  (IGH1M_MOUSE) -  Ig gamma-1 chain C region, membrane-bound form from Mus musculus

Seq: 393 a.a.

Struc: 220 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

DOI no: 10.1006/jmbi.1999.3101

J Mol Biol 292:855-869 (1999)

PubMed id: 10525411

Insight into odorant perception: the crystal structure and binding characteristics of antibody fragments directed against the musk odorant traseolide.

A.C.Langedijk, S.Spinelli, C.Anguille, P.Hermans, J.Nederlof, J.Butenandt, A.Honegger, C.Cambillau, A.Plückthun.

ABSTRACT

Monoclonal antibodies were elicited against the small hydrophobic hapten traseolide, a commercially available musk fragrance. Antibody variable region sequences were found to belong to different sequence groups, and the binding characteristics of the corresponding antibody fragments were investigated. The antibodies M02/01/01 and M02/05/01 are highly homologous and differ in the binding pocket only at position H93. M02/05/01 (H93 Val) binds the hapten traseolide about 75-fold better than M02/01/01 (H93 Ala). A traseolide analog, missing only one methyl group, does not have the characteristic musk odorant fragrance. The antibody M02/05/01 binds this hapten analog about tenfold less tightly than the original traseolide hapten, and mimics the odorant receptor in this respect, while the antibody M02/01/01 does not distinguish between the analog and traseolide. To elucidate the structural basis for the fine specificity of binding, we determined the crystal structure of the Fab fragment of M02/05/01 complexed with the hapten at 2.6 A resolution. The crystal structure showed that only van der Waals interactions are involved in binding. The somatic Ala H93 Val mutation in M02/05/01 fills up an empty cavity in the binding pocket. This leads to an increase in binding energy and to the ability to discriminate between the hapten traseolide and its derivatives. The structural understanding of odorant specificity in an antibody gives insight in the physical principles on how specificity for such hydrophobic molecules may be achieved.

Selected figure(s)

Figure 4.
Figure 4. Views (90 °) of the electron density map contoured at 1 sigma around the traseolide molecule and the combining site.

Figure 6.
Figure 6. The molecular surface of the Fab fragment at the combining site and of the hapten. (a) View of a molecular slice of the complex, emphasizing the non- perfect complementarity of the surfaces. (b) Orientation of the traseolide molecule in the combining site groove. The surface is colored according to the curvature.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1999, 292, 855-869) copyright 1999.

Figures were selected by an automated process.