Framework residue 71 is a major determinant of the position and conformation of the second hypervariable region in the VH domains of immunoglobulins

Anna Tramontano, Cyrus Chothia, Arthur Lesk

Research output: Contribution to journalArticle

203 Citations (Scopus)

Abstract

Analysis of the immunoglobulins of known structure reveals systematic differences in the position and main-chain conformation of the second hypervariable region of the VH domain (H2). We show that the major determinant of the position of H2 is the size of the residue at site 71, a site that is in the conserved framework of the VH domain. It is likely that for about two thirds of the known VH sequences the size of the residue at this site is also a major determinant of the conformation of H2. This effect can override the predisposition of the sequence, as in the case of the H2 loop of J539, which is an exception to the rules relating sequence and conformation of short hairpin loops. Understanding the relationship between the residue at position 71 and the position and conformation of H2 has applications to the prediction and engineering of antigen-binding sites of immunoglobulins.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalJournal of Molecular Biology
Volume215
Issue number1
DOIs
StatePublished - Sep 5 1990

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Immunoglobulins
Binding Sites
Antigens
Immunoglobulin Domains

All Science Journal Classification (ASJC) codes

  • Molecular Biology

Cite this

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abstract = "Analysis of the immunoglobulins of known structure reveals systematic differences in the position and main-chain conformation of the second hypervariable region of the VH domain (H2). We show that the major determinant of the position of H2 is the size of the residue at site 71, a site that is in the conserved framework of the VH domain. It is likely that for about two thirds of the known VH sequences the size of the residue at this site is also a major determinant of the conformation of H2. This effect can override the predisposition of the sequence, as in the case of the H2 loop of J539, which is an exception to the rules relating sequence and conformation of short hairpin loops. Understanding the relationship between the residue at position 71 and the position and conformation of H2 has applications to the prediction and engineering of antigen-binding sites of immunoglobulins.",
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Framework residue 71 is a major determinant of the position and conformation of the second hypervariable region in the VH domains of immunoglobulins. / Tramontano, Anna; Chothia, Cyrus; Lesk, Arthur.

In: Journal of Molecular Biology, Vol. 215, No. 1, 05.09.1990, p. 175-182.

Research output: Contribution to journalArticle

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