1W0R

Solution structure of dimeric form of properdin by X-ray solution scattering and analytical ultracentrifugation

1W0R の概要

• エントリーDOI: 10.2210/pdb1w0r/pdb
• 関連するPDBエントリー: 1W0S
• 分子名称: PROPERDIN (1 entity in total)
• 機能のキーワード: x-ray scattering, analytical ultracentrifugation, complement, thrombospondin type i repeats, constrained modelling, glycoprotein
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Secreted: P27918
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 97108.00

構造登録者

Sun, Z.,Reid, K.B.M.,Perkins, S.J. (登録日: 2004-06-09, 公開日: 2005-07-06, 最終更新日: 2024-05-08)

主引用文献

Sun, Z.,Reid, K.B.M.,Perkins, S.J.
The Dimeric and Trimeric Solution Structures of the Multidomain Complement Protein Properdin by X-Ray Scattering, Analytical Ultracentrifugation and Constrained Modelling.
J.Mol.Biol., 343:1327-, 2004

PubMed Abstract: Properdin regulates the alternative pathway of the complement system of immune defence by stabilising the C3 convertase complex. It contains six thrombospondin repeat type I (TSR-1 to TSR-6) domains and an N-terminal domain. Properdin exists as either a dimer, trimer or tetramer. In order to determine the solution structure of multiple TSR domains, the molecular structures of dimeric and trimeric properdin were studied by X-ray scattering and analytical ultracentrifugation. Guinier analyses showed that the dimer and trimer have radii of gyration R(G) values of 7.5 nm and 10.3 nm, respectively, and cross-sectional radii of gyration R(XS) values of 1.3 nm and 1.5 nm, respectively. Distance distribution functions showed that the maximum lengths of the dimer and trimer were 25 nm and 30 nm, respectively. Analytical ultracentrifugation gave sedimentation coefficients of 5.1S and 5.2S for the dimer and trimer forms, respectively. Homology models for the TSR domains were constructed using the crystal structure of the TSP-2 and TSP-3 domains in human thrombospondin as templates. Properdin could be represented by seven TSR domains, not six as believed, since the crystal structure determined for TSP-2 and TSP-3 showed that the N-terminal domain (TSR-0) could be represented by a truncated TSR domain with the same six conserved Cys residues found in TSR-1 to TSR-6. Automated constrained molecular modelling revealed the solution conformations of multiple TSR domains in properdin at medium resolution. The comparison of 3125 systematically generated conformational models for the trimer with the X-ray data showed that good curve fits could be obtained by assuming that the linker between adjacent TSR domains possessed limited flexibility. Good trimer models correspond to partially collapsed triangular structures, and extended triangular shapes do not fit the data. The corresponding 3125 models for the dimer revealed a similar outcome in which a partially collapsed TSR structure gave good fits. The models account for the effect of mutations that cause properdin deficiencies, and suggest that the biologically active TSR-4, TSR-5 and TSR-6 domains are exposed for protein-protein interactions. The role of the other TSR domains in properdin may be to act as spacers to make TSR-4, TSR-5 and TSR-6 accessible for function.

PubMed: 15491616
DOI: 10.1016/J.JMB.2004.09.001

実験手法

SOLUTION SCATTERING