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PDBsum entry 2pn5
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Immune system
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PDB id
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2pn5
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References listed in PDB file
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Key reference
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Title
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Structural basis for conserved complement factor-Like function in the antimalarial protein tep1.
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Authors
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R.H.Baxter,
C.I.Chang,
Y.Chelliah,
S.Blandin,
E.A.Levashina,
J.Deisenhofer.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
11615-11620.
[DOI no: ]
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PubMed id
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Abstract
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Thioester-containing proteins (TEPs) are a major component of the innate immune
response of insects to invasion by bacteria and protozoa. TEPs form a distinct
clade of a superfamily that includes the pan-protease inhibitors
alpha(2)-macroglobulins and vertebrate complement factors. The essential feature
of these proteins is a sequestered thioester bond that, after cleavage in a
protease-sensitive region of the protein, is activated and covalently binds to
its target. Recently, TEP1 from the malarial vector Anopheles gambiae was shown
to mediate recognition and killing of ookinetes from the malarial parasite
Plasmodium berghei, a model for the human malarial parasite Plasmodium
falciparum. Here, we present the crystal structure of the TEP1 isoform TEP1r.
Although the overall protein fold of TEP1r resembles that of complement factor
C3, the TEP1r domains are repositioned to stabilize the inactive conformation of
the molecule (containing an intact thioester) in the absence of the
anaphylotoxin domain, a central component of complement factors. The structure
of TEP1r provides a molecular basis for the differences between TEP1 alleles
TEP1r and TEP1s, which correlate with resistance of A. gambiae to infection by
P. berghei.
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Figure 1.
Fig. 1. Overall structure of TEP1r. (A) Domain arrangements
of TEP1r in comparison with human C3 (PDB ID 2A73). The mature
protein commences with domain MG1 (medium blue) followed by MG2
(orange), MG3 (purple), MG4 (medium gray), MG5 (light green),
MG6 (pink), LNK (light brown), MG7 (light blue), CUB (navy
blue), TED (dark green), MG8 (yellow), and ANK (light gray).
Additional domains in C3 are the ANA domain (red, between MG3
and MG8) and the C345C domain (dark red, top). (B) Sequence
schematic of TEP1r, showing disposition of domains. (C) The
relative position of MG3 to MG7-MG8 in TEP1r compared with human
C3.
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Figure 2.
Fig. 2. Stereo figure with refined density. 2F[o]–F[c]
density (cyan) contoured at 1  for the MG3/MG8
interface.
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