Conformational analysis of the first observed non-proline cis-peptide bond occurring within the complementarity determining region (CDR) of an antibody

• Published in: Journal of molecular biology Vol. 284; no. 3; pp. 549 - 555
• Main Authors: Bates, Paul A, Dokurno, Pawel, Freemont, Paul S, Sternberg, Michael J.E
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 04.12.1998
• Subjects: anti-tumour antibody; Antibodies - chemistry; Crystallography, X-Ray; Databases, Factual; Immunoglobulin Variable Region - chemistry; Models, Molecular; non-proline cis-peptide bond; novel antibody to peptide recognition; Peptides - chemistry; Proline - chemistry; Protein Conformation; CDR; anti-tumour antibody; novel antibody to peptide recognition; VL, VH; RMSD; H3; non-proline cis-peptide bond; PDB
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1006/jmbi.1998.2210

An analysis has been performed on the first example of a non-proline cis-peptide bond found within a complementarity determining region (CDR) of an antibody. The bond is located in CDR 3 of the heavy chain (H3) and makes substantial interactions to a peptide from a breast tumour-associated antigen. The antibody-peptide complex is compared, both in H3 length (six residues) and peptide conformation, to a number of other such complexes in the Brookhaven Data Bank (PDB). There is only one other H3 loop of the same length. Analysis of loop searches of the PDB, taken over the H3 framework of SM3, suggest that there is a limited repertoire of conformations for loops of length 6 compared to loops of length 5 and 7. It is argued that the cis-peptide bond is present because of the limited number of loop conformations of length 6, plus, the requirement of the H3 loop to contact the bound peptide. Modelling suggests that an all- trans-peptide loop conformation can replace the H3 loop and this raises the question of whether there is a trans- to cis-peptide bond isomerization upon peptide binding.