PDBsum entry 4p3b

Immune system

PDB id: 4p3b

Contents

Protein chains

69 a.a.

Ligands

FMT ×15

Waters ×204

PDB id:

4p3b

Name:

Immune system

Title:

Crystal structure of the mouse c5a-desarg anaphylatoxin

Structure:

Complement c5. Chain: a, b, c, d. Fragment: unp residues 679-754. Synonym: hemolytic complement. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: c5, hc. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.10Å R-factor: 0.183 R-free: 0.224

Authors:

L.Yatime,J.A.Schatz-Jakobsen,G.R.Andersen

Key ref:

J.A.Schatz-Jakobsen et al. (2014). Structural and functional characterization of human and murine C5a anaphylatoxins. Acta Crystallogr D Biol Crystallogr, 70, 1704-1717. PubMed id: 24914981 DOI: 10.1107/S139900471400844X

Date:

06-Mar-14 Release date: 11-Jun-14

Protein chains

P06684  (CO5_MOUSE) -  Complement C5 from Mus musculus

Seq: 1680 a.a.

Struc: 69 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1107/S139900471400844X

Acta Crystallogr D Biol Crystallogr 70:1704-1717 (2014)

PubMed id: 24914981

Structural and functional characterization of human and murine C5a anaphylatoxins.

J.A.Schatz-Jakobsen, L.Yatime, C.Larsen, S.V.Petersen, A.Klos, G.R.Andersen.

ABSTRACT

Complement is an ancient part of the innate immune system that plays a pivotal role in protection against invading pathogens and helps to clear apoptotic and necrotic cells. Upon complement activation, a cascade of proteolytic events generates the complement effectors, including the anaphylatoxins C3a and C5a. Signalling through their cognate G-protein coupled receptors, C3aR and C5aR, leads to a wide range of biological events promoting inflammation at the site of complement activation. The function of anaphylatoxins is regulated by circulating carboxypeptidases that remove their C-terminal arginine residue, yielding C3a-desArg and C5a-desArg. Whereas human C3a and C3a-desArg adopt a canonical four-helix bundle fold, the conformation of human C5a-desArg has recently been described as a three-helix bundle. Here, the crystal structures of an antagonist version of human C5a, A8(Δ71-73), and of murine C5a and C5a-desArg are reported. Whereas A8(Δ71-73) adopts a three-helix bundle conformation similar to human C5a-desArg, the two murine proteins form a four-helix bundle. A cell-based functional assay reveals that murine C5a-desArg, in contrast to its human counterpart, exerts the same level of activition as murine C5a on its cognate receptor. The role of the different C5a conformations is discussed in relation to the differential activation of C5a receptors across species.