PDBsum entry 2a55

Immune system

PDB id: 2a55

Contents

Protein chain

133 a.a. *

* Residue conservation analysis

PDB id:

2a55

Name:

Immune system

Title:

Solution structure of the two n-terminal ccp modules of c4b-binding protein (c4bp) alpha-chain.

Structure:

C4b-binding protein. Chain: a. Fragment: modules 1 and 2 of c4bp alpha-chain, residues 49-126. Synonym: c4bp, proline-rich protein, prp. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: c4bpa. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

40 models

Authors:

H.T.Jenkins,L.Mark,G.Ball,G.Lindahl,D.Uhrin,A.M.Blom,P.N.Barlow

Key ref:

H.T.Jenkins et al. (2006). Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor. J Biol Chem, 281, 3690-3697. PubMed id: 16330538 DOI: 10.1074/jbc.M511563200

Date:

30-Jun-05 Release date: 13-Dec-05

Protein chain

P04003  (C4BPA_HUMAN) -  C4b-binding protein alpha chain from Homo sapiens

Seq: 597 a.a.

Struc: 133 a.a.*

* PDB and UniProt seqs differ at 9 residue positions (black crosses)

DOI no: 10.1074/jbc.M511563200

J Biol Chem 281:3690-3697 (2006)

PubMed id: 16330538

Human C4b-binding protein, structural basis for interaction with streptococcal M protein, a major bacterial virulence factor.

H.T.Jenkins, L.Mark, G.Ball, J.Persson, G.Lindahl, D.Uhrin, A.M.Blom, P.N.Barlow.

ABSTRACT

Human C4b-binding protein (C4BP) protects host tissue, and those pathogens able to hijack this plasma glycoprotein, from complement-mediated destruction. We now show that the first two complement control protein (CCP) modules of the C4BP alpha-chain, plus the four residues connecting them, are necessary and sufficient for binding a bacterial virulence factor, the Streptococcus pyogenes M4 (Arp4) protein. Structure determination by NMR reveals two tightly coupled CCP modules in an elongated arrangement within this region of C4BP. Chemical shift perturbation studies demonstrate that the N-terminal, hypervariable region of M4 binds to a site including strand 1 of CCP module 2. This interaction is accompanied by an intermodular reorientation within C4BP. We thus provide a detailed picture of an interaction whereby a pathogen evades complement.

Selected figure(s)

Figure 4.
Titration of C4BP12 with M4-N. Overlay of five ^15N-^1H HSQC spectra of 20 μmC4BP12 (20 mm NaOAc, pH 6.0, 37 °C) with increasing concentrations of M4-N. Colors are as follows: black, 0 μm M4-N; red, 10 μm M4-N; purple, 25 μm M4-N; blue, 50 μm M4-N; navy, 100 μm M4-N (all concentrations are for the dimer). Cross-peaks from residues altered in the mutagenesis studies are labeled.

Figure 5.
Surface representations of C4BP12. The closest to mean structure of residues 1-124 is shown. A, surface representation, indicating residues that show chemical shift changes upon M4-N binding. Blue, small combined chemical shift difference (see below); red, large chemical shift difference, unable to track cross-peak. Residues for which no ^NH shift information could be obtained (either proline residues or due to overlap in the HSQC spectra) are colored gray. B, electrostatic surface potential, Calculated using the Adaptive Poisson-Boltzmann Solver (49) plug-in within PyMOL: red is negative charge, and blue is positive charge. A range of -5/+5 kT was used. Those amino acids substituted in a mutagenesis study are marked. C, same view of the surface (transparent with backbone trace underneath) with residues that show chemical shift changes upon M4-N binding colored according to position: yellow, close to the interface (the chemical shift of these could be influenced by intermodular reorientation or direct contact); cyan, residues away from the interface likely to be in direct contact with M4-N. The aromatic side chains of Tyr^37, Tyr^62, and Phe^84 are shown in space-fill representation. D, sequence of C4BP12 illustrating the ^NH chemical shift changes on addition of M4-N. The residues are colored as follows: black, no apparent change (combined chemical shift difference √((Δδ^NH)^2 + (Δδ^15N/5)^2 < 0.08 ppm); gray, data missing; blue, small shift (combined chemical shift difference of >0.08 ppm, <0.2 ppm but able to trace peak movement); red, large shift (unable to track peak). All figures produced using PyMOL (http://www.pymol.org).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2006, 281, 3690-3697) copyright 2006.

Figures were selected by an automated process.