The three-dimensional structures of a polysaccharide binding antibody to cryptococcus neoformans and its complex with a peptide from a phage display library

Implications for the identification of peptide mimotopes

Aideen C M Young, Philippe Valadon, Arturo Casadevall, Matthew D. Scharff, James C. Sacchettini

Research output: Contribution to journalArticle

Abstract

The three-dimensional structure of 2H1, a protective monoclonal antibody to Cryptococcus neoformans, has been solved at 2.4 Å resolution, in both its unbound form and in complex with the 12 amino acid residue peptide PA1 (GLQYTPSWMLVG). PA1 was previously identified as a potential mimotope of the cryptococcal capsular polysaccharide by screening of a phage display peptide library. Peptide binding is associated with only minor rearrangements of some side-chains and a small shift in the H2 loop of the antibody. The peptide assumes a tightly coiled conformation consisting of one inverse γ-turn and one type II β-turn that serves to place the entire peptide motif, consisting of Thr(P5) Pro(P6), Trp(P8) Met(P9) and Leu(P10), into a depression in the antibody combining site. A small number of H-bonds between peptide and antibody contribute to the affinity and specificity. Poor steric complementarity between PA1 and the antibody heavy chain along with the fact that the majority of the interactions between 2H1 and PA1 involve van der Waals interactions with the light chain may explain why this peptide acts as only a partial mimotope of the capsular polysaccharide epitope.

Original languageEnglish (US)
Pages (from-to)622-634
Number of pages13
JournalJournal of Molecular Biology
Volume274
Issue number4
DOIs
StatePublished - Dec 12 1997
Externally publishedYes

Fingerprint

Peptide Library
Cryptococcus neoformans
Polysaccharides
Peptides
Antibodies
Epitopes
Binding Sites
Monoclonal Antibodies
Light
Amino Acids

Keywords

  • Antibody structure
  • Cryptococcus
  • Peptide
  • Phage library
  • Polysaccharide

ASJC Scopus subject areas

  • Virology

Cite this

The three-dimensional structures of a polysaccharide binding antibody to cryptococcus neoformans and its complex with a peptide from a phage display library : Implications for the identification of peptide mimotopes. / Young, Aideen C M; Valadon, Philippe; Casadevall, Arturo; Scharff, Matthew D.; Sacchettini, James C.

In: Journal of Molecular Biology, Vol. 274, No. 4, 12.12.1997, p. 622-634.

Research output: Contribution to journalArticle

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