Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Protein Science : A Publication of the Protein Society logoLink to Protein Science : A Publication of the Protein Society
. 2000 Sep;9(9):1607–1617. doi: 10.1110/ps.9.9.1607

Collectin structure: a review.

K Håkansson 1, K B Reid 1
PMCID: PMC2144709  PMID: 11045608

Abstract

Collectins are animal calcium dependent lectins that target the carbohydrate structures on invading pathogens, resulting in the agglutination and enhanced clearance of the microorganism. These proteins form trimers that may assemble into larger oligomers. Each polypeptide chain consists of four regions: a relatively short N-terminal region, a collagen like region, an alpha-helical coiled-coil, and the lectin domain. Only primary structure data are available for the N-terminal region, while the most important features of the collagen-like region can be derived from its homology with collagen. The structures of the alpha-helical coiled-coil and the lectin domain are known from crystallographic studies of mannan binding protein (MBP) and lung surfactant protein D (SP-D). Carbohydrate binding has been structurally characterized in several complexes between MBP and carbohydrate; all indicate that the major interaction between carbohydrate and collectin is the binding of two adjacent carbohydrate hydroxyl group to a collectin calcium ion. In addition, these hydroxyl groups hydrogen bond to some of the calcium amino acid ligands. While each collectin trimer contains three such carbohydrate binding sites, deviation from the overall threefold symmetry has been demonstrated for SP-D, which may influence its binding properties. The protein surface between the three binding sites is positively charged in both MBP and SP-D.

Full Text

The Full Text of this article is available as a PDF (2.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beck K., Brodsky B. Supercoiled protein motifs: the collagen triple-helix and the alpha-helical coiled coil. J Struct Biol. 1998;122(1-2):17–29. doi: 10.1006/jsbi.1998.3965. [DOI] [PubMed] [Google Scholar]
  2. Bella J., Eaton M., Brodsky B., Berman H. M. Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution. Science. 1994 Oct 7;266(5182):75–81. doi: 10.1126/science.7695699. [DOI] [PubMed] [Google Scholar]
  3. Bernstein F. C., Koetzle T. F., Williams G. J., Meyer E. F., Jr, Brice M. D., Rodgers J. R., Kennard O., Shimanouchi T., Tasumi M. The Protein Data Bank: a computer-based archival file for macromolecular structures. J Mol Biol. 1977 May 25;112(3):535–542. doi: 10.1016/s0022-2836(77)80200-3. [DOI] [PubMed] [Google Scholar]
  4. Bertrand J. A., Pignol D., Bernard J. P., Verdier J. M., Dagorn J. C., Fontecilla-Camps J. C. Crystal structure of human lithostathine, the pancreatic inhibitor of stone formation. EMBO J. 1996 Jun 3;15(11):2678–2684. [PMC free article] [PubMed] [Google Scholar]
  5. Burling F. T., Weis W. I., Flaherty K. M., Brünger A. T. Direct observation of protein solvation and discrete disorder with experimental crystallographic phases. Science. 1996 Jan 5;271(5245):72–77. doi: 10.1126/science.271.5245.72. [DOI] [PubMed] [Google Scholar]
  6. Colley K. J., Baenziger J. U. Identification of the post-translational modifications of the core-specific lectin. The core-specific lectin contains hydroxyproline, hydroxylysine, and glucosylgalactosylhydroxylysine residues. J Biol Chem. 1987 Jul 25;262(21):10290–10295. [PubMed] [Google Scholar]
  7. Crouch E. C. Collectins and pulmonary host defense. Am J Respir Cell Mol Biol. 1998 Aug;19(2):177–201. doi: 10.1165/ajrcmb.19.2.140. [DOI] [PubMed] [Google Scholar]
  8. Crouch E., Persson A., Chang D., Heuser J. Molecular structure of pulmonary surfactant protein D (SP-D). J Biol Chem. 1994 Jun 24;269(25):17311–17319. [PubMed] [Google Scholar]
  9. Drickamer K. Engineering galactose-binding activity into a C-type mannose-binding protein. Nature. 1992 Nov 12;360(6400):183–186. doi: 10.1038/360183a0. [DOI] [PubMed] [Google Scholar]
  10. Elhalwagi B. M., Damodarasamy M., McCormack F. X. Alternate amino terminal processing of surfactant protein A results in cysteinyl isoforms required for multimer formation. Biochemistry. 1997 Jun 10;36(23):7018–7025. doi: 10.1021/bi970100q. [DOI] [PubMed] [Google Scholar]
  11. Engel J., Prockop D. J. The zipper-like folding of collagen triple helices and the effects of mutations that disrupt the zipper. Annu Rev Biophys Biophys Chem. 1991;20:137–152. doi: 10.1146/annurev.bb.20.060191.001033. [DOI] [PubMed] [Google Scholar]
  12. Graves B. J., Crowther R. L., Chandran C., Rumberger J. M., Li S., Huang K. S., Presky D. H., Familletti P. C., Wolitzky B. A., Burns D. K. Insight into E-selectin/ligand interaction from the crystal structure and mutagenesis of the lec/EGF domains. Nature. 1994 Feb 10;367(6463):532–538. doi: 10.1038/367532a0. [DOI] [PubMed] [Google Scholar]
  13. Gronwald W., Loewen M. C., Lix B., Daugulis A. J., Sönnichsen F. D., Davies P. L., Sykes B. D. The solution structure of type II antifreeze protein reveals a new member of the lectin family. Biochemistry. 1998 Apr 7;37(14):4712–4721. doi: 10.1021/bi972788c. [DOI] [PubMed] [Google Scholar]
  14. Holmskov U., Laursen S. B., Malhotra R., Wiedemann H., Timpl R., Stuart G. R., Tornøe I., Madsen P. S., Reid K. B., Jensenius J. C. Comparative study of the structural and functional properties of a bovine plasma C-type lectin, collectin-43, with other collectins. Biochem J. 1995 Feb 1;305(Pt 3):889–896. doi: 10.1042/bj3050889. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Holmskov U., Lawson P., Teisner B., Tornoe I., Willis A. C., Morgan C., Koch C., Reid K. B. Isolation and characterization of a new member of the scavenger receptor superfamily, glycoprotein-340 (gp-340), as a lung surfactant protein-D binding molecule. J Biol Chem. 1997 May 23;272(21):13743–13749. doi: 10.1074/jbc.272.21.13743. [DOI] [PubMed] [Google Scholar]
  16. Hoppe H. J., Reid K. B. Trimeric C-type lectin domains in host defence. Structure. 1994 Dec 15;2(12):1129–1133. doi: 10.1016/S0969-2126(94)00115-4. [DOI] [PubMed] [Google Scholar]
  17. Håkansson K., Lim N. K., Hoppe H. J., Reid K. B. Crystal structure of the trimeric alpha-helical coiled-coil and the three lectin domains of human lung surfactant protein D. Structure. 1999 Mar 15;7(3):255–264. doi: 10.1016/s0969-2126(99)80036-7. [DOI] [PubMed] [Google Scholar]
  18. Iobst S. T., Drickamer K. Binding of sugar ligands to Ca(2+)-dependent animal lectins. II. Generation of high-affinity galactose binding by site-directed mutagenesis. J Biol Chem. 1994 Jun 3;269(22):15512–15519. [PubMed] [Google Scholar]
  19. Kolatkar A. R., Leung A. K., Isecke R., Brossmer R., Drickamer K., Weis W. I. Mechanism of N-acetylgalactosamine binding to a C-type animal lectin carbohydrate-recognition domain. J Biol Chem. 1998 Jul 31;273(31):19502–19508. doi: 10.1074/jbc.273.31.19502. [DOI] [PubMed] [Google Scholar]
  20. Kolatkar A. R., Weis W. I. Structural basis of galactose recognition by C-type animal lectins. J Biol Chem. 1996 Mar 22;271(12):6679–6685. [PubMed] [Google Scholar]
  21. Kramer R. Z., Bella J., Mayville P., Brodsky B., Berman H. M. Sequence dependent conformational variations of collagen triple-helical structure. Nat Struct Biol. 1999 May;6(5):454–457. doi: 10.1038/8259. [DOI] [PubMed] [Google Scholar]
  22. Kramer R. Z., Vitagliano L., Bella J., Berisio R., Mazzarella L., Brodsky B., Zagari A., Berman H. M. X-ray crystallographic determination of a collagen-like peptide with the repeating sequence (Pro-Pro-Gly). J Mol Biol. 1998 Jul 24;280(4):623–638. doi: 10.1006/jmbi.1998.1881. [DOI] [PubMed] [Google Scholar]
  23. Kurata H., Sannoh T., Kozutsumi Y., Yokota Y., Kawasaki T. Structure and function of mannan-binding proteins isolated from human liver and serum. J Biochem. 1994 Jun;115(6):1148–1154. doi: 10.1093/oxfordjournals.jbchem.a124471. [DOI] [PubMed] [Google Scholar]
  24. Lee Y. M., Leiby K. R., Allar J., Paris K., Lerch B., Okarma T. B. Primary structure of bovine conglutinin, a member of the C-type animal lectin family. J Biol Chem. 1991 Feb 15;266(5):2715–2723. [PubMed] [Google Scholar]
  25. Lu J. H., Thiel S., Wiedemann H., Timpl R., Reid K. B. Binding of the pentamer/hexamer forms of mannan-binding protein to zymosan activates the proenzyme C1r2C1s2 complex, of the classical pathway of complement, without involvement of C1q. J Immunol. 1990 Mar 15;144(6):2287–2294. [PubMed] [Google Scholar]
  26. Lu J. Collectins: collectors of microorganisms for the innate immune system. Bioessays. 1997 Jun;19(6):509–518. doi: 10.1002/bies.950190610. [DOI] [PubMed] [Google Scholar]
  27. Lu J., Wiedemann H., Timpl R., Reid K. B. Similarity in structure between C1q and the collectins as judged by electron microscopy. Behring Inst Mitt. 1993 Dec;(93):6–16. [PubMed] [Google Scholar]
  28. Malhotra R., Laursen S. B., Willis A. C., Sim R. B. Localization of the receptor-binding site in the collectin family of proteins. Biochem J. 1993 Jul 1;293(Pt 1):15–19. doi: 10.1042/bj2930015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Matsushita M., Fujita T. Activation of the classical complement pathway by mannose-binding protein in association with a novel C1s-like serine protease. J Exp Med. 1992 Dec 1;176(6):1497–1502. doi: 10.1084/jem.176.6.1497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. McCormack F. X., Calvert H. M., Watson P. A., Smith D. L., Mason R. J., Voelker D. R. The structure and function of surfactant protein A. Hydroxyproline- and carbohydrate-deficient mutant proteins. J Biol Chem. 1994 Feb 25;269(8):5833–5841. [PubMed] [Google Scholar]
  31. McCormack F. X., Damodarasamy M., Elhalwagi B. M. Deletion mapping of N-terminal domains of surfactant protein A. The N-terminal segment is required for phospholipid aggregation and specific inhibition of surfactant secretion. J Biol Chem. 1999 Jan 29;274(5):3173–3181. doi: 10.1074/jbc.274.5.3173. [DOI] [PubMed] [Google Scholar]
  32. McCormack F. X., Pattanajitvilai S., Stewart J., Possmayer F., Inchley K., Voelker D. R. The Cys6 intermolecular disulfide bond and the collagen-like region of rat SP-A play critical roles in interactions with alveolar type II cells and surfactant lipids. J Biol Chem. 1997 Oct 31;272(44):27971–27979. doi: 10.1074/jbc.272.44.27971. [DOI] [PubMed] [Google Scholar]
  33. Mizuno H., Fujimoto Z., Koizumi M., Kano H., Atoda H., Morita T. Structure of coagulation factors IX/X-binding protein, a heterodimer of C-type lectin domains. Nat Struct Biol. 1997 Jun;4(6):438–441. doi: 10.1038/nsb0697-438. [DOI] [PubMed] [Google Scholar]
  34. Ng K. K., Drickamer K., Weis W. I. Structural analysis of monosaccharide recognition by rat liver mannose-binding protein. J Biol Chem. 1996 Jan 12;271(2):663–674. doi: 10.1074/jbc.271.2.663. [DOI] [PubMed] [Google Scholar]
  35. Ng K. K., Park-Snyder S., Weis W. I. Ca2+-dependent structural changes in C-type mannose-binding proteins. Biochemistry. 1998 Dec 22;37(51):17965–17976. doi: 10.1021/bi981972a. [DOI] [PubMed] [Google Scholar]
  36. Ng K. K., Weis W. I. Structure of a selectin-like mutant of mannose-binding protein complexed with sialylated and sulfated Lewis(x) oligosaccharides. Biochemistry. 1997 Feb 4;36(5):979–988. doi: 10.1021/bi962564e. [DOI] [PubMed] [Google Scholar]
  37. Nielsen B. B., Kastrup J. S., Rasmussen H., Holtet T. L., Graversen J. H., Etzerodt M., Thøgersen H. C., Larsen I. K. Crystal structure of tetranectin, a trimeric plasminogen-binding protein with an alpha-helical coiled coil. FEBS Lett. 1997 Jul 28;412(2):388–396. doi: 10.1016/s0014-5793(97)00664-9. [DOI] [PubMed] [Google Scholar]
  38. Ohtani K., Suzuki Y., Eda S., Kawai T., Kase T., Yamazaki H., Shimada T., Keshi H., Sakai Y., Fukuoh A. Molecular cloning of a novel human collectin from liver (CL-L1). J Biol Chem. 1999 May 7;274(19):13681–13689. doi: 10.1074/jbc.274.19.13681. [DOI] [PubMed] [Google Scholar]
  39. Persson A., Chang D., Rust K., Moxley M., Longmore W., Crouch E. Purification and biochemical characterization of CP4 (SP-D), a collagenous surfactant-associated protein. Biochemistry. 1989 Jul 25;28(15):6361–6367. doi: 10.1021/bi00441a031. [DOI] [PubMed] [Google Scholar]
  40. Poget S. F., Legge G. B., Proctor M. R., Butler P. J., Bycroft M., Williams R. L. The structure of a tunicate C-type lectin from Polyandrocarpa misakiensis complexed with D -galactose. J Mol Biol. 1999 Jul 23;290(4):867–879. doi: 10.1006/jmbi.1999.2910. [DOI] [PubMed] [Google Scholar]
  41. Quesenberry M. S., Drickamer K. Role of conserved and nonconserved residues in the Ca(2+)-dependent carbohydrate-recognition domain of a rat mannose-binding protein. Analysis by random cassette mutagenesis. J Biol Chem. 1992 May 25;267(15):10831–10841. [PubMed] [Google Scholar]
  42. Rothmann A. B., Mortensen H. D., Holmskov U., Højrup P. Structural characterization of bovine collectin-43. Eur J Biochem. 1997 Feb 1;243(3):630–635. doi: 10.1111/j.1432-1033.1997.t01-1-00630.x. [DOI] [PubMed] [Google Scholar]
  43. Sano K., Fisher J., Mason R. J., Kuroki Y., Schilling J., Benson B., Voelker D. Isolation and sequence of a cDNA clone for the rat pulmonary surfactant-associated protein (PSP-A). Biochem Biophys Res Commun. 1987 Apr 14;144(1):367–374. doi: 10.1016/s0006-291x(87)80519-3. [DOI] [PubMed] [Google Scholar]
  44. Sheriff S., Chang C. Y., Ezekowitz R. A. Human mannose-binding protein carbohydrate recognition domain trimerizes through a triple alpha-helical coiled-coil. Nat Struct Biol. 1994 Nov;1(11):789–794. doi: 10.1038/nsb1194-789. [DOI] [PubMed] [Google Scholar]
  45. Thiel S., Vorup-Jensen T., Stover C. M., Schwaeble W., Laursen S. B., Poulsen K., Willis A. C., Eggleton P., Hansen S., Holmskov U. A second serine protease associated with mannan-binding lectin that activates complement. Nature. 1997 Apr 3;386(6624):506–510. doi: 10.1038/386506a0. [DOI] [PubMed] [Google Scholar]
  46. Voss T., Eistetter H., Schäfer K. P., Engel J. Macromolecular organization of natural and recombinant lung surfactant protein SP 28-36. Structural homology with the complement factor C1q. J Mol Biol. 1988 May 5;201(1):219–227. doi: 10.1016/0022-2836(88)90448-2. [DOI] [PubMed] [Google Scholar]
  47. Wallis R., Drickamer K. Asymmetry adjacent to the collagen-like domain in rat liver mannose-binding protein. Biochem J. 1997 Jul 15;325(Pt 2):391–400. doi: 10.1042/bj3250391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Wallis R., Drickamer K. Molecular determinants of oligomer formation and complement fixation in mannose-binding proteins. J Biol Chem. 1999 Feb 5;274(6):3580–3589. doi: 10.1074/jbc.274.6.3580. [DOI] [PubMed] [Google Scholar]
  49. Weis W. I., Drickamer K., Hendrickson W. A. Structure of a C-type mannose-binding protein complexed with an oligosaccharide. Nature. 1992 Nov 12;360(6400):127–134. doi: 10.1038/360127a0. [DOI] [PubMed] [Google Scholar]
  50. Weis W. I., Drickamer K. Structural basis of lectin-carbohydrate recognition. Annu Rev Biochem. 1996;65:441–473. doi: 10.1146/annurev.bi.65.070196.002301. [DOI] [PubMed] [Google Scholar]
  51. Weis W. I., Drickamer K. Trimeric structure of a C-type mannose-binding protein. Structure. 1994 Dec 15;2(12):1227–1240. doi: 10.1016/S0969-2126(94)00124-3. [DOI] [PubMed] [Google Scholar]
  52. Weis W. I., Kahn R., Fourme R., Drickamer K., Hendrickson W. A. Structure of the calcium-dependent lectin domain from a rat mannose-binding protein determined by MAD phasing. Science. 1991 Dec 13;254(5038):1608–1615. doi: 10.1126/science.1721241. [DOI] [PubMed] [Google Scholar]
  53. Zhang M., Damodarasamy M., Elhalwagi B. M., McCormack F. X. The longer isoform and Cys-1 disulfide bridge of rat surfactant protein A are not essential for phospholipid and type II cell interactions. Biochemistry. 1998 Nov 24;37(47):16481–16488. doi: 10.1021/bi9817966. [DOI] [PubMed] [Google Scholar]
  54. van Eijk M., Haagsman H. P., Skinner T., Archibald A., Reid K. B., Lawson P. R., Archibold A. Porcine lung surfactant protein D: complementary DNA cloning, chromosomal localization, and tissue distribution. J Immunol. 2000 Feb 1;164(3):1442–1450. doi: 10.4049/jimmunol.164.3.1442. [DOI] [PubMed] [Google Scholar]

Articles from Protein Science : A Publication of the Protein Society are provided here courtesy of The Protein Society

RESOURCES