Canonical structures for the hypervariable regions of immunoglobulins

Cyrus Chothia, Arthur Lesk

Research output: Contribution to journalArticle

1069 Citations (Scopus)

Abstract

We have analysed the atomic structures of Fab and VL fragments of immunoglobulins to determine the relationship between their amino acid sequences and the three-dimensional structures of their antigen binding sites. We identify the relatively few residues that, through their packing, hydrogen bonding or the ability to assume unusual φ, ψ or ω conformations, are primarily responsible for the main-chain conformations of the hypervariable regions. These residues are found to occur at sites within the hypervariable regions and in the conserved β-sheet framework. Examination of the sequences of immunoglobulins of unknown structure shows that many have hypervariable regions that are similar in size to one of the known structures and contain identical residues at the sites responsible for the observed conformation. This implies that these hypervariable regions have conformations close to those in the known structures. For five of the hypervariable regions, the repertoire of conformations appears to be limited to a relatively small number of discrete structural classes. We call the commonly occurring main-chain conformations of the hypervariable regions "canonical structures". The accuracy of the analysis is being tested and refined by the prediction of immunoglobulin structures prior to their experimental determination.

Original languageEnglish (US)
Pages (from-to)901-917
Number of pages17
JournalJournal of Molecular Biology
Volume196
Issue number4
DOIs
StatePublished - Aug 20 1987

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Complementarity Determining Regions
Immunoglobulins
Immunoglobulin Fab Fragments
Hydrogen Bonding
Amino Acid Sequence
Binding Sites
Antigens

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Cite this

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abstract = "We have analysed the atomic structures of Fab and VL fragments of immunoglobulins to determine the relationship between their amino acid sequences and the three-dimensional structures of their antigen binding sites. We identify the relatively few residues that, through their packing, hydrogen bonding or the ability to assume unusual φ, ψ or ω conformations, are primarily responsible for the main-chain conformations of the hypervariable regions. These residues are found to occur at sites within the hypervariable regions and in the conserved β-sheet framework. Examination of the sequences of immunoglobulins of unknown structure shows that many have hypervariable regions that are similar in size to one of the known structures and contain identical residues at the sites responsible for the observed conformation. This implies that these hypervariable regions have conformations close to those in the known structures. For five of the hypervariable regions, the repertoire of conformations appears to be limited to a relatively small number of discrete structural classes. We call the commonly occurring main-chain conformations of the hypervariable regions {"}canonical structures{"}. The accuracy of the analysis is being tested and refined by the prediction of immunoglobulin structures prior to their experimental determination.",
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Canonical structures for the hypervariable regions of immunoglobulins. / Chothia, Cyrus; Lesk, Arthur.

In: Journal of Molecular Biology, Vol. 196, No. 4, 20.08.1987, p. 901-917.

Research output: Contribution to journalArticle

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