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Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study.

Gilbert HE, Eaton JT, Hannan JP, Holers VM, Perkins SJ
J Mol Biol 346 859-73 (2005)
Cited: 44 times
EuropePMC logo PMID: 15713468

Abstract

Complement receptor type 2 (CR2, CD21) forms a tight complex with C3d, a fragment of C3, the major complement component. Previous crystal structures of the C3d-CR2 SCR 1-2 complex and free CR2 SCR 1-2 showed that the two SCR domains of CR2 form contact with each other in a closed V-shaped structure. SCR 1 and SCR 2 are connected by an unusually long eight-residue linker peptide. Medium-resolution solution structures for CR2 SCR 1-2, C3d, and their complex were determined by X-ray scattering and analytical ultracentrifugation. CR2 SCR 1-2 is monomeric. For CR2 SCR 1-2, its radius of gyration R(G) of 2.12(+/-0.05) nm, its maximum length of 10nm and its sedimentation coefficient s20,w(o) of 1.40(+/-0.03) S do not agree with those calculated from the crystal structures, and instead suggest an open structure. Computer modelling of the CR2 SCR1-2 solution structure was based on the structural randomisation of the eight-residue linker peptide joining SCR 1 and SCR 2 to give 9950 trial models. Comparisons with the X-ray scattering curve indicated that the most favoured arrangements for the two SCR domains corresponded to an open V-shaped structure with no contacts between the SCR domains. For C3d, X-ray scattering and sedimentation velocity experiments showed that it exists as a monomer-dimer equilibrium with a dissociation constant of 40 microM. The X-ray scattering curve for monomeric C3d gave an R(G) value of 1.95 nm, and this together with its s20,w(o) value of 3.17 S gave good agreement with the monomeric C3d crystal structure. Modelling of the C3d dimer gave good agreements with its scattering and ultracentrifugation parameters. For the complex, scattering and ultracentrifugation experiments showed that there was no dimerisation, indicating that the C3d dimerisation site was located close to the CR2 SCR 1-2 binding site. The R(G) value of 2.44(+/-0.1) nm, its length of 9 nm and its s20,w(o) value of 3.45(+/-0.01) S showed that its structure was not much more elongated than that of C3d. Calculations with 9950 models of CR2 SCR 1-2 bound to C3d through SCR 2 showed that SCR 1 formed an open V-shaped structure with SCR 2 and was capable of interacting with the surface of C3d. We conclude that the open V-shaped structures formed by CR2 SCR 1-2, both when free and when bound to C3d, are optimal for the formation of a tight two-domain interaction with its ligand C3d.

Reviews - 1w2s mentioned but not cited (1)

  1. Structural biology of complement receptors. Santos-López J, de la Paz K, Fernández FJ, Vega MC. Front Immunol 14 1239146 (2023)

Articles - 1w2s mentioned but not cited (1)

  1. Cutting edge: members of the Staphylococcus aureus extracellular fibrinogen-binding protein family inhibit the interaction of C3d with complement receptor 2. Ricklin D, Ricklin-Lichtsteiner SK, Markiewski MM, Geisbrecht BV, Lambris JD. J. Immunol. 181 7463-7467 (2008)


Reviews citing this publication (7)

  1. X-ray solution scattering (SAXS) combined with crystallography and computation: defining accurate macromolecular structures, conformations and assemblies in solution. Putnam CD, Hammel M, Hura GL, Tainer JA. Q. Rev. Biophys. 40 191-285 (2007)
  2. Complement driven by conformational changes. Gros P, Milder FJ, Janssen BJ. Nat. Rev. Immunol. 8 48-58 (2008)
  3. Complement amplification revisited. Lutz HU, Jelezarova E. Mol. Immunol. 43 2-12 (2006)
  4. Complement factor H-ligand interactions: self-association, multivalency and dissociation constants. Perkins SJ, Nan R, Li K, Khan S, Miller A. Immunobiology 217 281-297 (2012)
  5. Structural insights into the central complement component C3. Janssen BJ, Gros P. Mol. Immunol. 44 3-10 (2007)
  6. Complement receptor 2, natural antibodies and innate immunity: Inter-relationships in B cell selection and activation. Holers VM, Kulik L. Mol. Immunol. 44 64-72 (2007)
  7. Deciphering complement mechanisms: the contributions of structural biology. Arlaud GJ, Barlow PN, Gaboriaud C, Gros P, Narayana SV. Mol. Immunol. 44 3809-3822 (2007)

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  2. The interactive Factor H-atypical hemolytic uremic syndrome mutation database and website: update and integration of membrane cofactor protein and Factor I mutations with structural models. Saunders RE, Abarrategui-Garrido C, Frémeaux-Bacchi V, Goicoechea de Jorge E, Goodship TH, López Trascasa M, Noris M, Ponce Castro IM, Remuzzi G, Rodríguez de Córdoba S, Sánchez-Corral P, Skerka C, Zipfel PF, Perkins SJ. Hum. Mutat. 28 222-234 (2007)
  3. Complement factor H binds at two independent sites to C-reactive protein in acute phase concentrations. Okemefuna AI, Nan R, Miller A, Gor J, Perkins SJ. J. Biol. Chem. 285 1053-1065 (2010)
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  5. Electrostatic interactions contribute to the folded-back conformation of wild type human factor H. Okemefuna AI, Nan R, Gor J, Perkins SJ. J. Mol. Biol. 391 98-118 (2009)
  6. The regulatory SCR-1/5 and cell surface-binding SCR-16/20 fragments of factor H reveal partially folded-back solution structures and different self-associative properties. Okemefuna AI, Gilbert HE, Griggs KM, Ormsby RJ, Gordon DL, Perkins SJ. J. Mol. Biol. 375 80-101 (2008)
  7. Associative and structural properties of the region of complement factor H encompassing the Tyr402His disease-related polymorphism and its interactions with heparin. Fernando AN, Furtado PB, Clark SJ, Gilbert HE, Day AJ, Sim RB, Perkins SJ. J. Mol. Biol. 368 564-581 (2007)
  8. Mutational analysis of the complement receptor type 2 (CR2/CD21)-C3d interaction reveals a putative charged SCR1 binding site for C3d. Hannan JP, Young KA, Guthridge JM, Asokan R, Szakonyi G, Chen XS, Holers VM. J. Mol. Biol. 346 845-858 (2005)
  9. Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: implications for the controversy regarding the CR2/C3d cocrystal structure. Isenman DE, Leung E, Mackay JD, Bagby S, van den Elsen JM. J Immunol 184 1946-1955 (2010)
  10. App1: an antiphagocytic protein that binds to complement receptors 3 and 2. Stano P, Williams V, Villani M, Cymbalyuk ES, Qureshi A, Huang Y, Morace G, Luberto C, Tomlinson S, Del Poeta M. J. Immunol. 182 84-91 (2009)
  11. The 15 SCR flexible extracellular domains of human complement receptor type 2 can mediate multiple ligand and antigen interactions. Gilbert HE, Asokan R, Holers VM, Perkins SJ. J. Mol. Biol. 362 1132-1147 (2006)
  12. The partly folded back solution structure arrangement of the 30 SCR domains in human complement receptor type 1 (CR1) permits access to its C3b and C4b ligands. Furtado PB, Huang CY, Ihyembe D, Hammond RA, Marsh HC, Perkins SJ. J. Mol. Biol. 375 102-118 (2008)
  13. Constrained solution scattering modelling of human antibodies and complement proteins reveals novel biological insights. Perkins SJ, Okemefuna AI, Nan R, Li K, Bonner A. J R Soc Interface 6 Suppl 5 S679-96 (2009)
  14. Molecular dynamics simulations of wild type and mutants of human complement receptor 2 complexed with C3d. Wan H, Hu JP, Tian XH, Chang S. Phys Chem Chem Phys 15 1241-1251 (2013)
  15. Solution structure of the complex formed between human complement C3d and full-length complement receptor type 2. Li K, Okemefuna AI, Gor J, Hannan JP, Asokan R, Holers VM, Perkins SJ. J. Mol. Biol. 384 137-150 (2008)
  16. Immunophysical properties and prediction of activities for vaccinia virus complement control protein and smallpox inhibitor of complement enzymes using molecular dynamics and electrostatics. Zhang L, Morikis D. Biophys. J. 90 3106-3119 (2006)
  17. Electrostatic contributions drive the interaction between Staphylococcus aureus protein Efb-C and its complement target C3d. Haspel N, Ricklin D, Geisbrecht BV, Kavraki LE, Lambris JD. Protein Sci. 17 1894-1906 (2008)
  18. Masking of the Fc region in human IgG4 by constrained X-ray scattering modelling: implications for antibody function and therapy. Abe Y, Gor J, Bracewell DG, Perkins SJ, Dalby PA. Biochem. J. 432 101-111 (2010)
  19. C-reactive protein exists in an NaCl concentration-dependent pentamer-decamer equilibrium in physiological buffer. Okemefuna AI, Stach L, Rana S, Buetas AJ, Gor J, Perkins SJ. J. Biol. Chem. 285 1041-1052 (2010)
  20. Immunophysical exploration of C3d-CR2(CCP1-2) interaction using molecular dynamics and electrostatics. Zhang L, Mallik B, Morikis D. J. Mol. Biol. 369 567-583 (2007)
  21. Self-association and domain rearrangements between complement C3 and C3u provide insight into the activation mechanism of C3. Li K, Gor J, Perkins SJ. Biochem. J. 431 63-72 (2010)
  22. Molecular basis of the interaction between complement receptor type 2 (CR2/CD21) and Epstein-Barr virus glycoprotein gp350. Young KA, Herbert AP, Barlow PN, Holers VM, Hannan JP. J. Virol. 82 11217-11227 (2008)
  23. Extended and flexible domain solution structure of the extracellular matrix protein anosmin-1 by X-ray scattering, analytical ultracentrifugation and constrained modelling. Hu Y, Sun Z, Eaton JT, Bouloux PM, Perkins SJ. J. Mol. Biol. 350 553-570 (2005)
  24. The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation. Krishnan V, Xu Y, Macon K, Volanakis JE, Narayana SV. Acta Crystallogr D Biol Crystallogr 65 266-274 (2009)
  25. Multimeric interactions between complement factor H and its C3d ligand provide new insight on complement regulation. Okemefuna AI, Li K, Nan R, Ormsby RJ, Sadlon T, Gordon DL, Perkins SJ. J. Mol. Biol. 391 119-135 (2009)
  26. Zinc-induced self-association of complement C3b and Factor H: implications for inflammation and age-related macular degeneration. Nan R, Tetchner S, Rodriguez E, Pao PJ, Gor J, Lengyel I, Perkins SJ. J. Biol. Chem. 288 19197-19210 (2013)
  27. Near-planar solution structures of mannose-binding lectin oligomers provide insight on activation of lectin pathway of complement. Miller A, Phillips A, Gor J, Wallis R, Perkins SJ. J. Biol. Chem. 287 3930-3945 (2012)
  28. Automated computational framework for the analysis of electrostatic similarities of proteins. Kieslich CA, Morikis D, Yang J, Gunopulos D. Biotechnol. Prog. 27 316-325 (2011)
  29. Mapping of the C3d ligand binding site on complement receptor 2 (CR2/CD21) using nuclear magnetic resonance and chemical shift analysis. Kovacs JM, Hannan JP, Eisenmesser EZ, Holers VM. J. Biol. Chem. 284 9513-9520 (2009)
  30. Use of time-resolved FRET to validate crystal structure of complement regulatory complex between C3b and factor H (N terminus). Pechtl IC, Neely RK, Dryden DT, Jones AC, Barlow PN. Protein Sci. 20 2102-2112 (2011)
  31. A theoretical view of the C3d:CR2 binding controversy. Mohan RR, Gorham RD, Morikis D. Mol. Immunol. 64 112-122 (2015)
  32. Extended flexible linker structures in the complement chimaeric conjugate CR2-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy. Gilbert HE, Aslam M, Guthridge JM, Holers VM, Perkins SJ. J. Mol. Biol. 356 397-412 (2006)
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  34. Solution structure of TT30, a novel complement therapeutic agent, provides insight into its joint binding to complement C3b and C3d. Li K, Gor J, Holers VM, Storek MJ, Perkins SJ. J. Mol. Biol. 418 248-263 (2012)
  35. Insights Into the Structure-Function Relationships of Dimeric C3d Fragments. Wahid AA, Dunphy RW, Macpherson A, Gibson BG, Kulik L, Whale K, Back C, Hallam TM, Alkhawaja B, Martin RL, Meschede I, Laabei M, Lawson ADG, Holers VM, Watts AG, Crennell SJ, Harris CL, Marchbank KJ, van den Elsen JMH. Front Immunol 12 714055 (2021)


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