PDBsum entry 2pn5

Immune system

PDB id: 2pn5

Contents

Protein chain

1283 a.a. *

Ligands

NAG-NAG

NAG ×3

Metals

_NA ×3

Waters ×140

* Residue conservation analysis

PDB id:

2pn5

Name:

Immune system

Title:

Crystal structure of tep1r

Structure:

Thioester-containing protein i. Chain: a. Fragment: residues 22-1338. Synonym: tep1r. Engineered: yes

Source:

Anopheles gambiae. African malaria mosquito. Organism_taxid: 7165. Gene: tep-i. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_cell_line: high-five(tm). Other_details: expression in bac-to-bac system by invitrogen

Resolution:

2.70Å R-factor: 0.239 R-free: 0.275

Authors:

R.H.G.Baxter

Key ref:

R.H.Baxter et al. (2007). Structural basis for conserved complement factor-like function in the antimalarial protein TEP1. Proc Natl Acad Sci U S A, 104, 11615-11620. PubMed id: 17606907 DOI: 10.1073/pnas.0704967104

Date:

23-Apr-07 Release date: 24-Jul-07

Protein chain

C9XI66  (TEPR1_ANOGA) -  Thioester-containing protein 1 allele R1 from Anopheles gambiae

Seq: 1338 a.a.

Struc: 1283 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1073/pnas.0704967104

Proc Natl Acad Sci U S A 104:11615-11620 (2007)

PubMed id: 17606907

Structural basis for conserved complement factor-like function in the antimalarial protein TEP1.

R.H.Baxter, C.I.Chang, Y.Chelliah, S.Blandin, E.A.Levashina, J.Deisenhofer.

ABSTRACT

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.

Selected figure(s)

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.

Figure 2.
Fig. 2. Stereo figure with refined density. 2F[o]–F[c] density (cyan) contoured at 1 for the MG3/MG8 interface.

Figures were selected by an automated process.