Crystal structure of Caenorhabditis elegans HER-1 characterization of the interaction between HER-1 and TRA-2A

Brent Y. Hamaoka, Charles E. Dann, Brian V. Geisbrecht, Daniel J. Leahy

Research output: Contribution to journalArticle

Abstract

HER-1 is a secreted protein that promotes male development in the nematode Caenorhabditis elegans. HER-1 inhibits the function of TRA-2A, a multipass integral membrane protein thought to serve as its receptor. We report here the 1.5-Å crystal structure of HER-1. The structure was solved by the multiwavelength anomalous diffraction method by using selenomethionyl- substituted HER-1 produced in Chinese hamster ovary cells. The HER-1 structure consists of two all-helical domains and is not closely homologous to any known structure. Sites of amino acid substitutions known to impair HER-1 function were mapped on the HER-1 structure and classified according to the likely mechanism by which they affect HER-1 activity. A subset of these and other amino acid substitutions on the HER-1 surface were assayed for their ability to disrupt interactions between HER-1 and TRA-2A-expressing cells, and a localized region on the HER-1 surface important for mediating this interaction was identified.

Original languageEnglish (US)
Pages (from-to)11673-11678
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number32
DOIs
StatePublished - Aug 10 2004

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Caenorhabditis elegans
Amino Acid Substitution
Cricetulus
Ovary
Membrane Proteins
Proteins

ASJC Scopus subject areas

  • Genetics
  • General

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Crystal structure of Caenorhabditis elegans HER-1 characterization of the interaction between HER-1 and TRA-2A. / Hamaoka, Brent Y.; Dann, Charles E.; Geisbrecht, Brian V.; Leahy, Daniel J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 101, No. 32, 10.08.2004, p. 11673-11678.

Research output: Contribution to journalArticle

Hamaoka, Brent Y. ; Dann, Charles E. ; Geisbrecht, Brian V. ; Leahy, Daniel J. / Crystal structure of Caenorhabditis elegans HER-1 characterization of the interaction between HER-1 and TRA-2A. In: Proceedings of the National Academy of Sciences of the United States of America. 2004 ; Vol. 101, No. 32. pp. 11673-11678.
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