PDBsum entry 4b2s

Immune system

PDB id: 4b2s

Contents

Protein chain

127 a.a.

PDB id:

4b2s

Name:

Immune system

Title:

Solution structure of ccp modules 11-12 of complement factor h

Structure:

Complement factor h. Chain: a. Fragment: ccps 11-12, residues 627-747. Synonym: h factor 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: komagataella pastoris. Expression_system_taxid: 4922.

NMR struc:

20 models

Authors:

E.Makou,H.D.Mertens,M.Maciejewski,D.C.Soares,I.Matis,C.Q.Schmidt, A.P.Herbert,D.I.Svergun,P.N.Barlow

Key ref:

E.Makou et al. (2012). Solution structure of CCP modules 10-12 illuminates functional architecture of the complement regulator, factor H. J Mol Biol, 424, 295-312. PubMed id: 23017427

Date:

17-Jul-12 Release date: 17-Oct-12

Protein chain

P08603  (CFAH_HUMAN) -  Complement factor H from Homo sapiens

Seq: 1231 a.a.

Struc: 127 a.a.*

* PDB and UniProt seqs differ at 6 residue positions (black crosses)

J Mol Biol 424:295-312 (2012)

PubMed id: 23017427

Solution structure of CCP modules 10-12 illuminates functional architecture of the complement regulator, factor H.

E.Makou, H.D.Mertens, M.Maciejewski, D.C.Soares, I.Matis, C.Q.Schmidt, A.P.Herbert, D.I.Svergun, P.N.Barlow.

ABSTRACT

The 155-kDa plasma glycoprotein factor H (FH), which consists of 20 complement control protein (CCP) modules, protects self-tissue but not foreign organisms from damage by the complement cascade. Protection is achieved by selective engagement of FH, via CCPs 1-4, CCPs 6-8 and CCPs 19-20, with polyanion-rich host surfaces that bear covalently attached, activation-specific, fragments of complement component C3. The role of intervening CCPs 9-18 in this process is obscured by lack of structural knowledge. We have concatenated new high-resolution solution structures of overlapping recombinant CCP pairs, 10-11 and 11-12, to form a three-dimensional structure of CCPs 10-12 and validated it by small-angle X-ray scattering of the recombinant triple-module fragment. Superimposing CCP 12 of this 10-12 structure with CCP 12 from the previously solved CCP 12-13 structure yielded an S-shaped structure for CCPs 10-13 in which modules are tilted by 80-110° with respect to immediate neighbors, but the bend between CCPs 10 and 11 is counter to the arc traced by CCPs 11-13. Including this four-CCP structure in interpretation of scattering data for the longer recombinant segments, CCPs 10-15 and 8-15, implied flexible attachment of CCPs 8 and 9 to CCP 10 but compact and intimate arrangements of CCP 14 with CCPs 12, 13 and 15. Taken together with difficulties in recombinant production of module pairs 13-14 and 14-15, the aberrant structure of CCP 13 and the variability of 13-14 linker sequences among orthologues, a structural dependency of CCP 14 on its neighbors is suggested; this has implications for the FH mechanism.