5HCC: Ternary Complex Of Human Complement C5 With Ornithodoros Moubata Omci And Dermacentor Andersoni Raci3

Citation:
Abstract
Activation of complement C5 generates the potent anaphylatoxin C5a and leads to pathogen lysis, inflammation and cell damage. The therapeutic potential of C5 inhibition has been demonstrated by eculizumab, one of the world's most expensive drugs. However, the mechanism of C5 activation by C5 convertases remains elusive, thus limiting development of therapeutics. Here we identify and characterize a new protein family of tick-derived C5 inhibitors. Structures of C5 in complex with the new inhibitors, the phase I and phase II inhibitor OmCI, or an eculizumab Fab reveal three distinct binding sites on C5 that all prevent activation of C5. The positions of the inhibitor-binding sites and the ability of all three C5-inhibitor complexes to competitively inhibit the C5 convertase conflict with earlier steric-inhibition models, thus suggesting that a priming event is needed for activation.
PDB ID: 5HCCDownload
MMDB ID: 137962
PDB Deposition Date: 2016/1/4
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 2.59  Å
Source Organism:
Dermacentor andersoni
Similar Structures:
Biological Unit for 5HCC: tetrameric; determined by author and by software (PISA)
Molecular Components in 5HCC
Label Count Molecule
Proteins (4 molecules)
1
Complement C5(Gene symbol: C5)
Molecule annotation
1
Complement C5(Gene symbol: C5)
Molecule annotation
1
Complement Inhibitor
Molecule annotation
1
Dermacentor Andersoni Raci3
Molecule annotation
Chemicals (10 molecules)
1
7
2
2
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.