A heterodimeric complex of the LRR proteins LRIM1 and APL1C regulates complement-like immunity in Anopheles gambiae

Richard H G Baxter, Stefanie Steinert, Yogarany Chelliah, Gloria Volohonsky, Elena A. Levashina, Johann Deisenhofer

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

The leucine-rich repeat (LRR) proteins LRIM1 and APL1C control the function of the complement-like protein TEP1 in Anopheles mosquitoes. The molecular structure of LRIM1 and APL1C and the basis of their interaction with TEP1 represent a new type of innate immune complex. The LRIM1/APL1C complex specifically binds and solubilizes a cleaved form of TEP1 without an intact thioester bond. The LRIM1 and APL1C LRR domains have a large radius of curvature, glycosylated concave face, and a novel C-terminal capping motif. The LRIM1/APL1C complex is a heterodimer with a single intermolecular disulfide bond. The structure of the LRIM1/APL1C heterodimer reveals an interface between the two LRR domains and an extensive C-terminal coiled-coil domain. We propose that a cleaved form of TEP1 may act as a convertase for activation of other TEP1 molecules and that the LRIM1/APL1C heterodimer regulates formation of this TEP1 convertase.

Original languageEnglish (US)
Pages (from-to)16817-16822
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number39
DOIs
Publication statusPublished - Sep 28 2010

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Keywords

  • Host-pathogen interactions
  • Innate immunity
  • Malaria
  • Thioester

ASJC Scopus subject areas

  • General
  • Medicine(all)

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