PDBsum entry 4xam

Immune system

PDB id: 4xam

Contents

Protein chains

651 a.a.

632 a.a.

281 a.a.

Superseded by:

5jtw

PDB id:

4xam

Name:

Immune system

Title:

Complement component c4b

Structure:

Complement c4 beta chain. Chain: a, b. Fragment: unp residues 20-675. Complement c4-a alpha chain. Chain: c, e. Fragment: unp residues 757-1446. Complement c4 gamma chain. Chain: d, f. Fragment: unp residues 1454-1744

Source:

Homo sapiens. Human. Organism_taxid: 9606. Tissue: blood. Tissue: blood

Resolution:

4.20Å R-factor: 0.219 R-free: 0.273

Authors:

S.Mortensen,R.T.Kidmose,S.V.Petersen,A.Szilagyi,G.R.Andersen

Key ref:

S.Mortensen et al. (2015). Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement. J Immunol, 194, 5488-5496. PubMed id: 25911760 DOI: 10.4049/jimmunol.1500087

Date:

15-Dec-14 Release date: 06-May-15

Protein chains

P0C0L4  (CO4A_HUMAN) -  Complement C4-A from Homo sapiens

Seq: 1744 a.a.

Struc: 651 a.a.

Protein chains

P0C0L4  (CO4A_HUMAN) -  Complement C4-A from Homo sapiens

Seq: 1744 a.a.

Struc: 632 a.a.*

Protein chains

P0C0L4  (CO4A_HUMAN) -  Complement C4-A from Homo sapiens

Seq: 1744 a.a.

Struc: 281 a.a.

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

DOI no: 10.4049/jimmunol.1500087

J Immunol 194:5488-5496 (2015)

PubMed id: 25911760

Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.

S.Mortensen, R.T.Kidmose, S.V.Petersen, �.�.Szilágyi, Z.Prohászka, G.R.Andersen.

ABSTRACT

Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5. In this article, we present the crystal and solution structures of the 195-kDa C4b. Our results provide the molecular details of the rearrangement accompanying C4 cleavage and suggest intramolecular flexibility of C4b. The conformations of C4b and its paralogue C3b are shown to be remarkably conserved, suggesting that the convertases from the classical and alternative pathways are likely to share their overall architecture and mode of substrate recognition. We propose an overall molecular model for the classical pathway C5 convertase in complex with C5, suggesting that C3b increases the affinity for the substrate by inducing conformational changes in C4b rather than a direct interaction with C5. C4b-specific features revealed by our structural studies are probably involved in the assembly of the classical pathway C3/C5 convertases and C4b binding to regulators.