TY - JOUR
T1 - A heterodimeric complex of the LRR proteins LRIM1 and APL1C regulates complement-like immunity in Anopheles gambiae
AU - Baxter, Richard H.G.
AU - Steinert, Stefanie
AU - Chelliah, Yogarany
AU - Volohonsky, Gloria
AU - Levashina, Elena A.
AU - Deisenhofer, Johann
PY - 2010/9/28
Y1 - 2010/9/28
N2 - 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.
AB - 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.
KW - Animals
KW - Anopheles/immunology
KW - Complement System Proteins/metabolism
KW - Crystallography, X-Ray
KW - Cysteine/metabolism
KW - Hemolymph/immunology
KW - Insect Proteins/chemistry
KW - Protein Conformation
KW - Protein Multimerization
KW - Protein Stability
KW - Recombinant Proteins/chemistry
UR - http://www.scopus.com/inward/record.url?scp=78049297909&partnerID=8YFLogxK
U2 - 10.1073/pnas.1010575107
DO - 10.1073/pnas.1010575107
M3 - Article
C2 - 20826443
AN - SCOPUS:78049297909
SN - 0027-8424
VL - 107
SP - 16817
EP - 16822
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 39
ER -
