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. 1993 Jun 1;121(5):1181–1189. doi: 10.1083/jcb.121.5.1181

Type V collagen: molecular structure and fibrillar organization of the chicken alpha 1(V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis

PMCID: PMC2119697  PMID: 8501123

Abstract

Previous work from our laboratories has demonstrated that: (a) the striated collagen fibrils of the corneal stroma are heterotypic structures composed of type V collagen molecules coassembled along with those of type I collagen, (b) the high content of type V collagen within the corneal collagen fibrils is one factor responsible for the small, uniform fibrillar diameter (25 nm) characteristic of this tissue, (c) the completely processed form of type V collagen found within tissues retains a large noncollagenous region, termed the NH2- terminal domain, at the amino end of its alpha 1 chain, and (d) the NH2- terminal domain may contain at least some of the information for the observed regulation of fibril diameters. In the present investigation we have employed polyclonal antibodies against the retained NH2- terminal domain of the alpha 1(V) chain for immunohistochemical studies of embryonic avian corneas and for immunoscreening a chicken cDNA library. When combined with cDNA sequencing and molecular rotary shadowing, these approaches provide information on the molecular structure of the retained NH2-terminal domain as well as how this domain might function in the regulation of fibrillar structure. In immunofluorescence and immunoelectron microscopy analyses, the antibodies against the NH2-terminal domain react with type V molecules present within mature heterotypic fibrils of the corneal stroma. Thus, epitopes within at least a portion of this domain are exposed on the fibril surface. This is in marked contrast to mAbs which we have previously characterized as being directed against epitopes located in the major triple helical domain of the type V molecule. The helical epitopes recognized by these antibodies are antigenically masked on type V molecules that have been assembled into fibrils. Sequencing of the isolated cDNA clones has provided the conceptual amino acid sequence of the entire amino end of the alpha 1(V) procollagen chain. The sequence shows the location of what appear to be potential propeptidase cleavage sites. One of these, if preferentially used during processing of the type V procollagen molecule, can provide an explanation for the retention of the NH2-terminal domain in the completely processed molecule. The sequencing data also suggest that the NH2-terminal domain consists of several regions, providing a structure which fits well with that of the completely processed type V molecule as visualized by rotary shadowing.

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Selected References

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  1. Birk D. E., Fitch J. M., Babiarz J. P., Doane K. J., Linsenmayer T. F. Collagen fibrillogenesis in vitro: interaction of types I and V collagen regulates fibril diameter. J Cell Sci. 1990 Apr;95(Pt 4):649–657. doi: 10.1242/jcs.95.4.649. [DOI] [PubMed] [Google Scholar]
  2. Birk D. E., Fitch J. M., Babiarz J. P., Linsenmayer T. F. Collagen type I and type V are present in the same fibril in the avian corneal stroma. J Cell Biol. 1988 Mar;106(3):999–1008. doi: 10.1083/jcb.106.3.999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Broek D. L., Madri J., Eikenberry E. F., Brodsky B. Characterization of the tissue form of type V collagen from chick bone. J Biol Chem. 1985 Jan 10;260(1):555–562. [PubMed] [Google Scholar]
  4. Bächinger H. P., Doege K. J., Petschek J. P., Fessler L. I., Fessler J. H. Structural implications from an electronmicroscopic comparison of procollagen V with procollagen I, pC-collagen I, procollagen IV, and a Drosophila procollagen. J Biol Chem. 1982 Dec 25;257(24):14590–14592. [PubMed] [Google Scholar]
  5. Chapman J. A. The regulation of size and form in the assembly of collagen fibrils in vivo. Biopolymers. 1989 Aug;28(8):1367–1382. doi: 10.1002/bip.360280803. [DOI] [PubMed] [Google Scholar]
  6. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  7. Doane K. J., Babiarz J. P., Fitch J. M., Linsenmayer T. F., Birk D. E. Collagen fibril assembly by corneal fibroblasts in three-dimensional collagen gel cultures: small-diameter heterotypic fibrils are deposited in the absence of keratan sulfate proteoglycan. Exp Cell Res. 1992 Sep;202(1):113–124. doi: 10.1016/0014-4827(92)90410-a. [DOI] [PubMed] [Google Scholar]
  8. Fessler L. I., Brosh S., Chapin S., Fessler J. H. Tyrosine sulfation in precursors of collagen V. J Biol Chem. 1986 Apr 15;261(11):5034–5040. [PubMed] [Google Scholar]
  9. Fessler L. I., Chapin S., Brosh S., Fessler J. H. Intracellular transport and tyrosine sulfation of procollagens V. Eur J Biochem. 1986 Aug 1;158(3):511–518. doi: 10.1111/j.1432-1033.1986.tb09784.x. [DOI] [PubMed] [Google Scholar]
  10. Fessler L. I., Kumamoto C. A., Meis M. E., Fessler J. H. Assembly and processing of procollagen V (AB) in chick blood vessels and other tissues. J Biol Chem. 1981 Sep 25;256(18):9640–9645. [PubMed] [Google Scholar]
  11. Fessler L. I., Shigaki N., Fessler J. H. Isolation of a new procollagen V chain from chick embryo tendon. J Biol Chem. 1985 Oct 25;260(24):13286–13293. [PubMed] [Google Scholar]
  12. Fitch J. M., Birk D. E., Mentzer A., Hasty K. A., Mainardi C., Linsenmayer T. F. Corneal collagen fibrils: dissection with specific collagenases and monoclonal antibodies. Invest Ophthalmol Vis Sci. 1988 Jul;29(7):1125–1136. [PubMed] [Google Scholar]
  13. Fitch J. M., Gibney E., Sanderson R. D., Mayne R., Linsenmayer T. F. Domain and basement membrane specificity of a monoclonal antibody against chicken type IV collagen. J Cell Biol. 1982 Nov;95(2 Pt 1):641–647. doi: 10.1083/jcb.95.2.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fitch J. M., Gross J., Mayne R., Johnson-Wint B., Linsenmayer T. F. Organization of collagen types I and V in the embryonic chicken cornea: monoclonal antibody studies. Proc Natl Acad Sci U S A. 1984 May;81(9):2791–2795. doi: 10.1073/pnas.81.9.2791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fleischmajer R., Olsen B. R., Timpl R., Perlish J. S., Lovelace O. Collagen fibril formation during embryogenesis. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3354–3358. doi: 10.1073/pnas.80.11.3354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fleischmajer R., Perlish J. S., Timpl R. Collagen fibrillogenesis in human skin. Ann N Y Acad Sci. 1985;460:246–257. doi: 10.1111/j.1749-6632.1985.tb51172.x. [DOI] [PubMed] [Google Scholar]
  17. Greenspan D. S., Cheng W., Hoffman G. G. The pro-alpha 1(V) collagen chain. Complete primary structure, distribution of expression, and comparison with the pro-alpha 1(XI) collagen chain. J Biol Chem. 1991 Dec 25;266(36):24727–24733. [PubMed] [Google Scholar]
  18. Gross J. Collagen biology: structure, degradation, and disease. Harvey Lect. 1974;68:351–432. [PubMed] [Google Scholar]
  19. Halila R., Peltonen L. Purification of human procollagen type III N-proteinase from placenta and preparation of antiserum. Biochem J. 1986 Oct 1;239(1):47–52. doi: 10.1042/bj2390047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hasty K. A., Pourmotabbed T. F., Goldberg G. I., Thompson J. P., Spinella D. G., Stevens R. M., Mainardi C. L. Human neutrophil collagenase. A distinct gene product with homology to other matrix metalloproteinases. J Biol Chem. 1990 Jul 15;265(20):11421–11424. [PubMed] [Google Scholar]
  21. Hortin G., Folz R., Gordon J. I., Strauss A. W. Characterization of sites of tyrosine sulfation in proteins and criteria for predicting their occurrence. Biochem Biophys Res Commun. 1986 Nov 26;141(1):326–333. doi: 10.1016/s0006-291x(86)80372-2. [DOI] [PubMed] [Google Scholar]
  22. Hörlein D., Fietzek P. P., Wachter E., Lapière C. M., Kühn K. Amino acid sequence of the aminoterminal segment of dermatosparactic calf-skin procollagen type I. Eur J Biochem. 1979 Aug 15;99(1):31–38. doi: 10.1111/j.1432-1033.1979.tb13227.x. [DOI] [PubMed] [Google Scholar]
  23. Ibrahim J., Harding J. J. Pinpointing the sites of hydroxylysine glycosides in peptide alpha 1-CB7 of bovine corneal collagen, and their possible role in determining fibril diameter and thus transparency. Biochim Biophys Acta. 1989 Jul 21;992(1):9–22. doi: 10.1016/0304-4165(89)90044-5. [DOI] [PubMed] [Google Scholar]
  24. Kadler K. E., Hulmes D. J., Hojima Y., Prockop D. J. Assembly of type I collagen fibrils de novo by the specific enzymic cleavage of pC collagen. The fibrils formed at about 37 degrees C are similar in diameter, roundness, and apparent flexibility to the collagen fibrils seen in connective tissue. Ann N Y Acad Sci. 1990;580:214–224. doi: 10.1111/j.1749-6632.1990.tb17930.x. [DOI] [PubMed] [Google Scholar]
  25. Keene D. R., Sakai L. Y., Burgeson R. E., Bächinger H. P. Direct visualization of IgM antibodies bound to tissue antigens using a monoclonal anti-type III collagen IgM as a model system. J Histochem Cytochem. 1987 Mar;35(3):311–318. doi: 10.1177/35.3.3546481. [DOI] [PubMed] [Google Scholar]
  26. Keene D. R., Sakai L. Y., Bächinger H. P., Burgeson R. E. Type III collagen can be present on banded collagen fibrils regardless of fibril diameter. J Cell Biol. 1987 Nov;105(5):2393–2402. doi: 10.1083/jcb.105.5.2393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kumamoto C. A., Fessler J. H. Propeptides of procollagen V (A,B) in chick embryo crop. J Biol Chem. 1981 Jul 10;256(13):7053–7058. [PubMed] [Google Scholar]
  28. Linsenmayer T. F., Fitch J. M., Gross J., Mayne R. Are collagen fibrils in the developing avian cornea composed of two different collagen types? Evidence from monoclonal antibody studies. Ann N Y Acad Sci. 1985;460:232–245. doi: 10.1111/j.1749-6632.1985.tb51171.x. [DOI] [PubMed] [Google Scholar]
  29. Linsenmayer T. F., Fitch J. M., Mayne R. Extracellular matrices in the developing avian eye: type V collagen in corneal and noncorneal tissues. Invest Ophthalmol Vis Sci. 1984 Jan;25(1):41–47. [PubMed] [Google Scholar]
  30. Linsenmayer T. F., Fitch J. M., Schmid T. M., Zak N. B., Gibney E., Sanderson R. D., Mayne R. Monoclonal antibodies against chicken type V collagen: production, specificity, and use for immunocytochemical localization in embryonic cornea and other organs. J Cell Biol. 1983 Jan;96(1):124–132. doi: 10.1083/jcb.96.1.124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mayne R., Wiedemann H., Irwin M. H., Sanderson R. D., Fitch J. M., Linsenmayer T. F., Kühn K. Monoclonal antibodies against chicken type IV and V collagens: electron microscopic mapping of the epitopes after rotary shadowing. J Cell Biol. 1984 May;98(5):1637–1644. doi: 10.1083/jcb.98.5.1637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. McLaughlin J. S., Linsenmayer T. F., Birk D. E. Type V collagen synthesis and deposition by chicken embryo corneal fibroblasts in vitro. J Cell Sci. 1989 Oct;94(Pt 2):371–379. doi: 10.1242/jcs.94.2.371. [DOI] [PubMed] [Google Scholar]
  33. Mendler M., Eich-Bender S. G., Vaughan L., Winterhalter K. H., Bruckner P. Cartilage contains mixed fibrils of collagen types II, IX, and XI. J Cell Biol. 1989 Jan;108(1):191–197. doi: 10.1083/jcb.108.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Morikawa T., Tuderman L., Prockop D. J. Inhibitors of procollagen N-protease. Synthetic peptides with sequences similar to the cleavage site in the pro alpha 1(I) chain. Biochemistry. 1980 Jun 10;19(12):2646–2650. doi: 10.1021/bi00553a017. [DOI] [PubMed] [Google Scholar]
  35. Peltonen L., Halila R., Ryhänen L. Enzymes converting procollagens to collagens. J Cell Biochem. 1985;28(1):15–21. doi: 10.1002/jcb.240280104. [DOI] [PubMed] [Google Scholar]
  36. Romanic A. M., Adachi E., Kadler K. E., Hojima Y., Prockop D. J. Copolymerization of pNcollagen III and collagen I. pNcollagen III decreases the rate of incorporation of collagen I into fibrils, the amount of collagen I incorporated, and the diameter of the fibrils formed. J Biol Chem. 1991 Jul 5;266(19):12703–12709. [PubMed] [Google Scholar]
  37. Sanger F., Coulson A. R. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J Mol Biol. 1975 May 25;94(3):441–448. doi: 10.1016/0022-2836(75)90213-2. [DOI] [PubMed] [Google Scholar]
  38. Scott J. E. Proteoglycan-fibrillar collagen interactions. Biochem J. 1988 Jun 1;252(2):313–323. doi: 10.1042/bj2520313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Su M. W., Suzuki H. R., Bieker J. J., Solursh M., Ramirez F. Expression of two nonallelic type II procollagen genes during Xenopus laevis embryogenesis is characterized by stage-specific production of alternatively spliced transcripts. J Cell Biol. 1991 Oct;115(2):565–575. doi: 10.1083/jcb.115.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Takahara K., Sato Y., Okazawa K., Okamoto N., Noda A., Yaoi Y., Kato I. Complete primary structure of human collagen alpha 1 (V) chain. J Biol Chem. 1991 Jul 15;266(20):13124–13129. [PubMed] [Google Scholar]
  41. Tseng S. C., Smuckler D., Stern R. Comparison of collagen types in adult and fetal bovine corneas. J Biol Chem. 1982 Mar 10;257(5):2627–2633. [PubMed] [Google Scholar]
  42. Vaughan L., Mendler M., Huber S., Bruckner P., Winterhalter K. H., Irwin M. I., Mayne R. D-periodic distribution of collagen type IX along cartilage fibrils. J Cell Biol. 1988 Mar;106(3):991–997. doi: 10.1083/jcb.106.3.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Woodbury D., Benson-Chanda V., Ramirez F. Amino-terminal propeptide of human pro-alpha 2(V) collagen conforms to the structural criteria of a fibrillar procollagen molecule. J Biol Chem. 1989 Feb 15;264(5):2735–2738. [PubMed] [Google Scholar]
  44. Wozney J., Hanahan D., Tate V., Boedtker H., Doty P. Structure of the pro alpha 2 (I) collagen gene. Nature. 1981 Nov 12;294(5837):129–135. doi: 10.1038/294129a0. [DOI] [PubMed] [Google Scholar]
  45. Wu H., Byrne M. H., Stacey A., Goldring M. B., Birkhead J. R., Jaenisch R., Krane S. M. Generation of collagenase-resistant collagen by site-directed mutagenesis of murine pro alpha 1(I) collagen gene. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5888–5892. doi: 10.1073/pnas.87.15.5888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. von Heijne G. Patterns of amino acids near signal-sequence cleavage sites. Eur J Biochem. 1983 Jun 1;133(1):17–21. doi: 10.1111/j.1432-1033.1983.tb07424.x. [DOI] [PubMed] [Google Scholar]

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