PDBsum entry 5fo8

Lipid binding

PDB id: 5fo8

Contents

Protein chains

639 a.a.

894 a.a.

129 a.a.

Ligands

NAG-NAG

NAG-NAG-BMA

EDO ×32

Waters ×492

PDB id:

5fo8

Name:

Lipid binding

Title:

Crystal structure of human complement c3b in complex with mcp (ccp1-4)

Structure:

Complement c3. Chain: a. Fragment: unp residues 23-667. Synonym: c3 and pzp-like alpha-2-macroglobulin domain-containing protein 1, c3adesarg, complement c3b. Complement c3. Chain: b. Fragment: unp residues 749-1663. Synonym: c3 and pzp-like alpha-2-macroglobulin domain-containing

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: purified from human plasma. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.40Å R-factor: 0.190 R-free: 0.219

Authors:

F.Forneris,J.Wu,X.Xue,P.Gros

Key ref:

F.Forneris et al. (2016). Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode. Embo J, 35, 1133-1149. PubMed id: 27013439 DOI: 10.15252/embj.201593673

Date:

18-Nov-15 Release date: 06-Apr-16

Protein chain

P01024  (CO3_HUMAN) -  Complement C3 from Homo sapiens

Seq: 1663 a.a.

Struc: 639 a.a.

Protein chain

P01024  (CO3_HUMAN) -  Complement C3 from Homo sapiens

Seq: 1663 a.a.

Struc: 894 a.a.*

Protein chain

P15529  (MCP_HUMAN) -  Membrane cofactor protein from Homo sapiens

Seq: 392 a.a.

Struc: 129 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.3.4.21.47 - alternative-complement-pathway C3/C5 convertase.
• Reaction: Cleaves C3 in the alpha-chain to yield C3a and C3b. Cleaves C5 in the alpha-chain to yield C5a and C5b. Both cleavages take place at the C-terminal of an arginine residue.

DOI no: 10.15252/embj.201593673

Embo J 35:1133-1149 (2016)

PubMed id: 27013439

Regulators of complement activity mediate inhibitory mechanisms through a common C3b-binding mode.

F.Forneris, J.Wu, X.Xue, D.Ricklin, Z.Lin, G.Sfyroera, A.Tzekou, E.Volokhina, J.C.Granneman, R.Hauhart, P.Bertram, M.K.Liszewski, J.P.Atkinson, J.D.Lambris, P.Gros.

ABSTRACT

Regulators of complement activation (RCA) inhibit complement-induced immune responses on healthy host tissues. We present crystal structures of human RCA (MCP, DAF, and CR1) and a smallpox virus homolog (SPICE) bound to complement component C3b. Our structural data reveal that up to four consecutive homologous CCP domains (i-iv), responsible for inhibition, bind in the same orientation and extended arrangement at a shared binding platform on C3b. Large sequence variations in CCP domains explain the diverse C3b-binding patterns, with limited or no contribution of some individual domains, while all regulators show extensive contacts with C3b for the domains at the third site. A variation of ~100° rotation around the longitudinal axis is observed for domains binding at the fourth site on C3b, without affecting the overall binding mode. The data suggest a common evolutionary origin for both inhibitory mechanisms, called decay acceleration and cofactor activity, with variable C3b binding through domains at sites ii, iii, and iv, and provide a framework for understanding RCA disease-related mutations and immune evasion.