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

Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16817-22. doi: 10.1073/pnas.1010575107. Epub 2010 Sep 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anopheles / immunology*
  • Complement System Proteins / metabolism*
  • Crystallography, X-Ray
  • Cysteine / metabolism
  • Hemolymph / immunology
  • Insect Proteins / chemistry
  • Insect Proteins / genetics
  • Insect Proteins / metabolism*
  • Protein Conformation
  • Protein Multimerization
  • Protein Stability
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Insect Proteins
  • LRIM1 protein, Anopheles gambiae
  • Recombinant Proteins
  • TEP1 protein, Anopheles gambiae
  • Complement System Proteins
  • Cysteine

Associated data

  • PDB/3O53
  • PDB/3O6N
  • PDB/3OJA