The origin of CDR H3 structural diversity

Brian D. Weitzner, Roland L. Dunbrack, Jeffrey J. Gray

Research output: Contribution to journalArticle

Abstract

Antibody complementarity determining region (CDR) H3 loops are critical for adaptive immunological functions. Although the other five CDR loops adopt predictable canonical structures, H3 conformations have proven unclassifiable, other than an unusual C-terminal "kink" present in most antibodies. To determine why the majority of H3 loops are kinked and to learn whether non-antibody proteins have loop structures similar to those of H3, we searched a set of 15,679 high-quality non-antibody structures for regions geometrically similar to the residues immediately surrounding the loop. By incorporating the kink into our search, we identified 1,030 H3-like loops from 632 protein families. Some protein families, including PDZ domains, appear to use the identified region for recognition and binding. Our results suggest that the kink is conserved in the immunoglobulin heavy chain fold because it disrupts the β-strand pairing at the base of the loop. Thus, the kink is a critical driver of the observed structural diversity in CDR H3.

Original languageEnglish (US)
Pages (from-to)302-311
Number of pages10
JournalStructure
Volume23
Issue number2
DOIs
StatePublished - Feb 3 2015

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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