2KMS

Combined high- and low-resolution techniques reveal compact structure in central portion of factor H despite long inter-modular linkers

2KMS の概要

• エントリーDOI: 10.2210/pdb2kms/pdb
• NMR情報: BMRB: 16439
• 分子名称: Complement factor H (1 entity in total)
• 機能のキーワード: compact structure, limited interdomain flexibility, age-related macular degeneration, alternative splicing, complement alternate pathway, disease mutation, disulfide bond, glycoprotein, immune response, innate immunity, polymorphism, secreted, sushi, immune system
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13262.05

構造登録者

Schmidt, C.Q.,Herbert, A.P.,Guariento, M.,Mertens, H.D.T.,Soares, D.C.,Uhrin, D.,Rowe, A.J.,Svergun, D.I.,Barlow, P.N. (登録日: 2009-08-04, 公開日: 2009-11-03, 最終更新日: 2024-11-13)

主引用文献

Schmidt, C.Q.,Herbert, A.P.,Mertens, H.D.T.,Guariento, M.,Soares, D.C.,Uhrin, D.,Rowe, A.J.,Svergun, D.I.,Barlow, P.N.
The Central Portion of Factor H (Modules 10-15) Is Compact and Contains a Structurally Deviant CCP Module
J.Mol.Biol., 395:105-122, 2010

PubMed Abstract: The first eight and the last two of 20 complement control protein (CCP) modules within complement factor H (fH) encompass binding sites for C3b and polyanionic carbohydrates. These binding sites cooperate self-surface selectively to prevent C3b amplification, thus minimising complement-mediated damage to host. Intervening fH CCPs, apparently devoid of such recognition sites, are proposed to play a structural role. One suggestion is that the generally small CCPs 10-15, connected by longer-than-average linkers, act as a flexible tether between the two functional ends of fH; another is that the long linkers induce a 180 degrees bend in the middle of fH. To test these hypotheses, we determined the NMR-derived structure of fH12-13 consisting of module 12, shown here to have an archetypal CCP structure, and module 13, which is uniquely short and features a laterally protruding helix-like insertion that contributes to a prominent electropositive patch. The unusually long fH12-13 linker is not flexible. It packs between the two CCPs that are not folded back on each other but form a shallow vee shape; analytical ultracentrifugation and X-ray scattering supported this finding. These two techniques additionally indicate that flanking modules (within fH11-14 and fH10-15) are at least as rigid and tilted relative to neighbours as are CCPs 12 and 13 with respect to one another. Tilts between successive modules are not unidirectional; their principal axes trace a zigzag path. In one of two arrangements for CCPs 10-15 that fit well with scattering data, CCP 14 is folded back onto CCP 13. In conclusion, fH10-15 forms neither a flexible tether nor a smooth bend. Rather, it is compact and has embedded within it a CCP module (CCP 13) that appears to be highly specialised given both its deviant structure and its striking surface charge distribution. A passive, purely structural role for this central portion of fH is unlikely.

PubMed: 19835885
DOI: 10.1016/j.jmb.2009.10.010

実験手法

SOLUTION NMR