PDBsum entry: 1xwe

Signaling protein

PDB-id: 1xwe

Contents

Description

Header details

Header records

References

PROCHECK

Protein chain

151 a.a. *

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

1xwe

Name:

Signaling protein

Title:

Nmr structure of c345c (ntr) domain of c5 of complement

Structure:

Complement c5. Chain: a. Fragment: c345c domain. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: c5. Expressed in: escherichia coli. Expression_system_taxid: 562.

UniProt:

P01031 (CO5_HUMAN)

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

Struc:

Seq:

1676 a.a.

Struc:

151 a.a.*

Key:

PfamA domain

Secondary structure

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Resolution:

not givenÅ

NMR structure:

40 models

Authors:

J.Bramham,C.-T.Thai,D.C.Soares,D.Uhrin,R.T.Ogata,P.N.Barlow

Key ref:

J.Bramham et al. (2005). Functional insights from the structure of the multifunctional C345C domain of C5 of complement.. J Biol Chem, 280, 10636-10645. [PubMed id: 15598652] [DOI: 10.1074/jbc.M413126200]

Date:

30-Oct-04

Release date:

21-Dec-04

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1074/jbc.M413126200

J Biol Chem 280:10636-10645 (2005)

PubMed id: 15598652

Functional insights from the structure of the multifunctional C345C domain of C5 of complement.

J.Bramham, C.T.Thai, D.C.Soares, D.Uhrín, R.T.Ogata, P.N.Barlow.

ABSTRACT

The complement protein C5 initiates assembly of the membrane attack complex. This remarkable process results in lysis of target cells and is fundamental to mammalian defense against infection. The 150-amino acid residue domain at the C terminus of C5 (C5-C345C) is pivotal to C5 function. It interacts with enzymes that convert C5 to C5b, the first step in the assembly of the membrane attack complex; it also binds to the membrane attack complex components C6 and C7 with high affinity. Here a recombinant version of this C5-C345C domain is shown to adopt the oligosaccharide/oligonucleotide binding fold, with two helices packed against a five-stranded beta-barrel. The structure is compared with those from the netrin-like module family that have a similar fold. Residues critical to the interaction with C5-convertase cluster on a mobile, hydrophobic inter-strand loop that protrudes from the open face of the beta-barrel. The opposite, helix-dominated face of C5-C345C carries a pair of exposed hydrophobic side chains adjacent to a striking negatively charged patch, consistent with affinity for positively charged factor I modules in C6 and C7. Modeling of homologous domains from complement proteins C3 and C4, which do not participate in membrane attack complex assembly, suggests that this provisionally identified C6/C7-interacting face is indeed specific to C5.

Selected figure(s)

Figure 1.
FIG. 1. Sequence alignments. A, structure-based sequence alignment of C345C/NTR domains. The alignment of C5-C345C with the C-terminal domain of PCOLCE-1, the N-terminal domain of agrin, and the N-terminal domains of TIMP-1 and TIMP-2 was generated using the program MATRAS (38). The extent of average secondary structure is represented above the sequences (solid, strand; hatched, helix), whereas residues within the C5 secondary structure are boxed. Buried (>95%) residues and surface-exposed (>30%) hydrophobic residues are indicated by filled squares and open squares, respectively. The disulfide linkages of C5 are shown. B, multiple sequence alignment of C345C from C3, C4, and C5 in a range of species. An initial multiple sequence alignment was derived using the program MUSCLE (28, 29) and edited manually. Residues in C5-C345C that are >95% buried are indicated by yellow highlighting. White letters against black indicate hydrophobic residues that are >30% surface-exposed. Gaps in chicken and rat sequences of C5 correspond to sequence information either missing from the data base or erroneously deposited/translated.

Figure 6.
FIG. 6. Electrostatic features of the C345C domains of C3, C4, and C5. A superposition of the homology-modeled C345C domains of C3 and C4 with the experimentally determined structure of C5-C345C (lowest NOE energy) is shown using schematics drawn in PyMol (top, left panel). The side chains of all Asp and Glu residues are drawn as sticks. Modules are color-coded as shown. The view is the same as in the left-hand panel of Fig. 3B. Other panels show electrostatic surfaces (generated using the Adaptive Poisson-Boltzmann Solver (40) plug-in within PyMol) of C5-C345C and of the modeled structures of the C345C domains of C3 and C4; red is negative charge, and blue is positive charge. A range of -4/+4 kT is used.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 10636-10645) copyright 2005.

Figures were selected by an automated process.