4B2S

Solution structure of CCP modules 11-12 of complement factor H

Summary for 4B2S

• Entry DOI: 10.2210/pdb4b2s/pdb
• Related: 1FHC 1HAQ 1HCC 1HFH 1HFI 1KOV 2G7I 2JGW 2JGX 2UWN 2V8E 2W80 2W81 2WII 2XQW 4AYD 4AYE 4AYI 4AYM 4B2R
• NMR Information: BMRB: 18599
• Descriptor: COMPLEMENT FACTOR H (1 entity in total)
• Functional Keywords: immune system, saxs, short consensus repeat
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Secreted: P08603
• Total number of polymer chains: 1
• Total formula weight: 14111.80

Authors

Makou, E.,Mertens, H.D.,Maciejewski, M.,Soares, D.C.,Matis, I.,Schmidt, C.Q.,Herbert, A.P.,Svergun, D.I.,Barlow, P.N. (deposition date: 2012-07-17, release date: 2012-10-17, Last modification date: 2024-10-16)

Primary citation

Makou, E.,Mertens, H.D.,Maciejewski, M.,Soares, D.C.,Matis, I.,Schmidt, C.Q.,Herbert, A.P.,Svergun, D.I.,Barlow, P.N.
Solution Structure of Ccp Modules 10-12 Illuminates Functional Architecture of the Complement Regulator, Factor H.
J.Mol.Biol., 424:295-, 2012

PubMed 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.

PubMed: 23017427
DOI: 10.1016/J.JMB.2012.09.013

Experimental method

SOLUTION NMR