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Biophysical Analysis of Anopheles gambiae Leucine-Rich Repeat Proteins APL1A1, APL1B and APL1C and Their Interaction with LRIM1

Year: 2015
Type: article
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.
Source: PLoS ONE
DOI: 10.1371/journal.pone.0118911
Institution: Yale University
Language: English
Subfield: Immunology
Open Access status: gold
Estimated APC paid: $2,382
Funders: U.S. Department of Energy, Office of Science, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Basic Energy Sciences, Biological and Environmental Research, Brookhaven National Laboratory, Lawrence Berkeley National Laboratory
Awards: G1126863173, G1286251239, G132563423, G1572106353, G2478636580, G3243759740, G338944111, G3897559065, G498139845, G5019921669, A. gambiae thioester-containing protein 1 (TEP1) protein-protein interactions, G5292656900, G5300179398, G549834383, G5693151484, MINOS (Macromolecular Insights on Nucleic acids Optimized by Scattering), G719843099, G7345354777, G7559664950, G8507651203, G969889393
OpenAlex ID: W2039596080
FWCI: 1.315
Cites: 59
Cited by: 16
Related to: 10