title: A heterodimeric complex of the LRR proteins LRIM1 and APL1C regulates complement-like immunity in Anopheles gambiae.
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.
authors.affiliation: Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390-9050, USA.
authors.forename: Richard H G
authors.initials: RH
authors.lastname: Baxter
authors.forename: Stefanie
authors.initials: S
authors.lastname: Steinert
authors.forename: Yogarany
authors.initials: Y
authors.lastname: Chelliah
authors.forename: Gloria
authors.initials: G
authors.lastname: Volohonsky
authors.forename: Elena A
authors.initials: EA
authors.lastname: Levashina
authors.forename: Johann
authors.initials: J
authors.lastname: Deisenhofer
mesh_terms: D000818:Animals; D000852:Anopheles / Q000276:immunology*; D003165:Complement System Proteins / Q000378:metabolism*; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000378:metabolism; D006458:Hemolymph / Q000276:immunology; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D055503:Protein Multimerization; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D019476:Insect Proteins; C540280:LRIM1 protein, Anopheles gambiae; D011994:Recombinant Proteins; C544265:TEP1 protein, Anopheles gambiae; D003165:Complement System Proteins; D003545:Cysteine
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