4P39

Crystal structure of the human C5aR antagonist C5a-A8

Summary for 4P39

• Entry DOI: 10.2210/pdb4p39/pdb
• Related: 3HQA 3HQB 4P3A 4P3B
• Descriptor: Complement C5 (2 entities in total)
• Functional Keywords: complement anaphylatoxin, c5a, three-helix bundle, gpcr antagonist, immune system
• Biological source: Homo sapiens (Human)
• Cellular location: Secreted: P01031
• Total number of polymer chains: 4
• Total formula weight: 33462.71

Authors

Yatime, L.,Schatz-Jakobsen, J.A.,Larsen, C.,Andersen, G.R. (deposition date: 2014-03-06, release date: 2014-06-11, Last modification date: 2024-10-16)

Primary citation

Schatz-Jakobsen, J.A.,Yatime, L.,Larsen, C.,Petersen, S.V.,Klos, A.,Andersen, G.R.
Structural and functional characterization of human and murine C5a anaphylatoxins.
Acta Crystallogr. D Biol. Crystallogr., 70:1704-1717, 2014

PubMed 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.

PubMed: 24914981
DOI: 10.1107/S139900471400844X

Experimental method

X-RAY DIFFRACTION (2.401 Å)