Structure-Function Analysis of the
LRIM1/APL1C Complex and its Interaction with Complement C3-Like Protein
TEP1
Malaria threatens half the world's population and exacts a devastating human
toll. The principal malaria vector in Africa, the mosquito Anopheles
gambiae, encodes 24 members of a recently identified family of
leucine-rich repeat proteins named LRIMs. Two members of this family, LRIM1 and
APL1C, are crucial components of the mosquito complement-like pathway that is
important for immune defense against Plasmodium parasites.
LRIM1 and APL1C circulate in the hemolymph exclusively as a disulfide-bonded
complex that specifically interacts with the mature form of the complement
C3-like protein, TEP1. We have investigated the specificity of LRIM1/APL1C
complex formation and which regions of these proteins are required for
interactions with TEP1. To address these questions, we have generated a set of
LRIM1 and APL1C alleles altering key conserved structural elements and assayed
them in cell culture for complex formation and interaction with TEP1. Our data
indicate that heterocomplex formation is an intrinsic ability of LRIM1 and APL1C
and identify key homologous cysteine residues forming the intermolecular
disulfide bond. We also demonstrate that the coiled-coil domain is the binding
site for TEP1 but also contributes to the specificity of LRIM1/APL1C complex
formation. In addition, we show that the LRIM1/APL1C complex interacts with the
mature forms of three other TEP proteins, one of which, TEP3, we have
characterized as a Plasmodium antagonist. We conclude that
LRIM1 and APL1C contain three distinct modules:
a C-terminal coiled-coil domain
that can carry different TEP protein cargoes, potentially with distinct
functions, a central cysteine-rich region that controls complex formation and an
N-terminal leucine-rich repeat with a putative role in pathogen recognition.
Vyšlo v časopise:
Structure-Function Analysis of the
LRIM1/APL1C Complex and its Interaction with Complement C3-Like Protein
TEP1. PLoS Pathog 7(4): e32767. doi:10.1371/journal.ppat.1002023
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1002023
Souhrn
Malaria threatens half the world's population and exacts a devastating human
toll. The principal malaria vector in Africa, the mosquito Anopheles
gambiae, encodes 24 members of a recently identified family of
leucine-rich repeat proteins named LRIMs. Two members of this family, LRIM1 and
APL1C, are crucial components of the mosquito complement-like pathway that is
important for immune defense against Plasmodium parasites.
LRIM1 and APL1C circulate in the hemolymph exclusively as a disulfide-bonded
complex that specifically interacts with the mature form of the complement
C3-like protein, TEP1. We have investigated the specificity of LRIM1/APL1C
complex formation and which regions of these proteins are required for
interactions with TEP1. To address these questions, we have generated a set of
LRIM1 and APL1C alleles altering key conserved structural elements and assayed
them in cell culture for complex formation and interaction with TEP1. Our data
indicate that heterocomplex formation is an intrinsic ability of LRIM1 and APL1C
and identify key homologous cysteine residues forming the intermolecular
disulfide bond. We also demonstrate that the coiled-coil domain is the binding
site for TEP1 but also contributes to the specificity of LRIM1/APL1C complex
formation. In addition, we show that the LRIM1/APL1C complex interacts with the
mature forms of three other TEP proteins, one of which, TEP3, we have
characterized as a Plasmodium antagonist. We conclude that
LRIM1 and APL1C contain three distinct modules:
a C-terminal coiled-coil domain
that can carry different TEP protein cargoes, potentially with distinct
functions, a central cysteine-rich region that controls complex formation and an
N-terminal leucine-rich repeat with a putative role in pathogen recognition.
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Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
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