Biophysical analysis of anopheles gambiae leucine-rich repeat proteins APL1A1, APL1B [corrected] and APL1C and their interaction with LRIM1

PLoS One. 2015 Mar 16;10(3):e0118911. doi: 10.1371/journal.pone.0118911. eCollection 2015.

Abstract

Natural infection of Anopheles gambiae by malaria-causing Plasmodium parasites is significantly influenced by the APL1 genetic locus. The locus contains three closely related leucine-rich repeat (LRR) genes, APL1A, APL1B and APL1C. Multiple studies have reported the participation of APL1A-C in the immune response of A. gambiae to invasion by both rodent and human Plasmodium isolates. APL1C forms a heterodimer with the related LRR protein LRIM1 via a C-terminal coiled-coil domain that is also present in APL1A and APL1B. The LRIM1/APL1C heterodimer protects A. gambiae from infection by binding the complement-like protein TEP1 to form a stable and active immune complex. Here we report solution x-ray scatting data for the LRIM1/APL1C heterodimer, the oligomeric state of LRIM1/APL1 LRR domains in solution and the crystal structure of the APL1B LRR domain. The LRIM1/APL1C heterodimeric complex has a flexible and extended structure in solution. In contrast to the APL1A, APL1C and LRIM1 LRR domains, the APL1B LRR domain is a homodimer. The crystal structure of APL1B-LRR shows that the homodimer is formed by an N-terminal helix that complements for the absence of an N-terminal capping motif in APL1B, which is a unique distinction within the LRIM1/APL1 protein family. Full-length APL1A1 and APL1B form a stable complex with LRIM1. These results support a model in which APL1A1, APL1B and APL1C can all form an extended, flexible heterodimer with LRIM1, providing a repertoire of functional innate immune complexes to protect A. gambiae from a diverse array of pathogens.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anopheles / chemistry*
  • Anopheles / immunology*
  • Anopheles / metabolism
  • Anopheles / parasitology
  • Humans
  • Insect Proteins / chemistry
  • Insect Proteins / genetics
  • Insect Proteins / immunology
  • Insect Proteins / metabolism*
  • Leucine-Rich Repeat Proteins
  • Malaria / transmission
  • Models, Molecular
  • Molecular Sequence Data
  • Plasmodium / physiology
  • Protein Conformation
  • Protein Interaction Maps*
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / immunology
  • Proteins / metabolism*
  • Sequence Alignment

Substances

  • Insect Proteins
  • LRIM1 protein, Anopheles gambiae
  • Leucine-Rich Repeat Proteins
  • Proteins