Promotion of cell adhesion by single-stranded and triple-helical peptide models of basement membrane collagen α1(IV)531-543. Evidence for conformationally dependent and conformationally independent type IV collagen cell adhesion sites

A. J. Miles, Amy P Skubitz, Leo T Furcht, G. B. Fields

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Abstract

Several regions within the triple-helical domain of type IV collagen function as cellular recognition sites. We have demonstrated previously that melanoma cell activities promoted by the α1(IV)1263-1277 sequences are enhanced by triple helicity (Fields, C. G., Mickelson, D. J., Drake, S. L., McCarthy, J. B., and Fields, G. B. (1993) J. Biol. Chem. 268, 14153-14160), whereas Eble et al. reached similar conclusions for α1β1 integrin-mediated fibrosarcoma cell adhesion to [α1(IV)]2α2(IV)434-472 (Eble, J. A., Golbik, R., Mann, K., and Kuhn, K. (1993) EMBO J. 12, 4795-4802). In the present study, we have examined the cell adhesion activities of a third region in type IV collagen. A single-stranded peptide (SSP) incorporating the α1(IV)531-543 sequence promoted the adhesion of melanoma, ovarian carcinoma, and Jurkat cells in a dose-dependent manner, with 40% cell adhesion observed at [SSP] = 1.8, 11.5, and 42.2 μM, respectively. Nearly identical results were obtained for cell adhesion to an all-D-enantiomer of the SSP, suggesting that the cell surface receptor(s) for this site do not discriminate based on chirality. The α1(IV)531-543 sequence maintained its cell adhesion promoting activity when incorporated into a homotrimeric triple-helical polypeptide, although relative levels of adhesion were either slightly enhanced or slightly diminished compared with the SSP. Triple-helical conformation was thus not critical for cellular recognition of the α1(IV)531-543 sequence. Single-site substitution experiments of the SSP showed no overall correlation between the biological effects of substitutions and SSP conformation. The SSP, D-SSP, triple-helical polypeptide, and SSP substitution results suggest that cell recognition of the α1(IV)531-543 sequence is generally independent of substrate conformation. The present and prior studies indicate that 'conformationally dependent' and 'conformationally independent' cellular recognition sites exist within the triple-helical domain of type IV collagen.

Original languageEnglish (US)
Pages (from-to)30939-30945
Number of pages7
JournalJournal of Biological Chemistry
Volume269
Issue number49
StatePublished - Jan 1 1994

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Collagen Type IV
Cell adhesion
Basement Membrane
Cell Adhesion
Collagen
Peptides
Conformations
Substitution reactions
Melanoma
Adhesion
Jurkat Cells
Enantiomers
Fibrosarcoma
Chirality
Cell Surface Receptors
Integrins
Carcinoma

Cite this

@article{231031cc6c93489ea255e162352bba52,
title = "Promotion of cell adhesion by single-stranded and triple-helical peptide models of basement membrane collagen α1(IV)531-543. Evidence for conformationally dependent and conformationally independent type IV collagen cell adhesion sites",
abstract = "Several regions within the triple-helical domain of type IV collagen function as cellular recognition sites. We have demonstrated previously that melanoma cell activities promoted by the α1(IV)1263-1277 sequences are enhanced by triple helicity (Fields, C. G., Mickelson, D. J., Drake, S. L., McCarthy, J. B., and Fields, G. B. (1993) J. Biol. Chem. 268, 14153-14160), whereas Eble et al. reached similar conclusions for α1β1 integrin-mediated fibrosarcoma cell adhesion to [α1(IV)]2α2(IV)434-472 (Eble, J. A., Golbik, R., Mann, K., and Kuhn, K. (1993) EMBO J. 12, 4795-4802). In the present study, we have examined the cell adhesion activities of a third region in type IV collagen. A single-stranded peptide (SSP) incorporating the α1(IV)531-543 sequence promoted the adhesion of melanoma, ovarian carcinoma, and Jurkat cells in a dose-dependent manner, with 40{\%} cell adhesion observed at [SSP] = 1.8, 11.5, and 42.2 μM, respectively. Nearly identical results were obtained for cell adhesion to an all-D-enantiomer of the SSP, suggesting that the cell surface receptor(s) for this site do not discriminate based on chirality. The α1(IV)531-543 sequence maintained its cell adhesion promoting activity when incorporated into a homotrimeric triple-helical polypeptide, although relative levels of adhesion were either slightly enhanced or slightly diminished compared with the SSP. Triple-helical conformation was thus not critical for cellular recognition of the α1(IV)531-543 sequence. Single-site substitution experiments of the SSP showed no overall correlation between the biological effects of substitutions and SSP conformation. The SSP, D-SSP, triple-helical polypeptide, and SSP substitution results suggest that cell recognition of the α1(IV)531-543 sequence is generally independent of substrate conformation. The present and prior studies indicate that 'conformationally dependent' and 'conformationally independent' cellular recognition sites exist within the triple-helical domain of type IV collagen.",
author = "Miles, {A. J.} and Skubitz, {Amy P} and Furcht, {Leo T} and Fields, {G. B.}",
year = "1994",
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language = "English (US)",
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journal = "Journal of Biological Chemistry",
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T1 - Promotion of cell adhesion by single-stranded and triple-helical peptide models of basement membrane collagen α1(IV)531-543. Evidence for conformationally dependent and conformationally independent type IV collagen cell adhesion sites

AU - Miles, A. J.

AU - Skubitz, Amy P

AU - Furcht, Leo T

AU - Fields, G. B.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - Several regions within the triple-helical domain of type IV collagen function as cellular recognition sites. We have demonstrated previously that melanoma cell activities promoted by the α1(IV)1263-1277 sequences are enhanced by triple helicity (Fields, C. G., Mickelson, D. J., Drake, S. L., McCarthy, J. B., and Fields, G. B. (1993) J. Biol. Chem. 268, 14153-14160), whereas Eble et al. reached similar conclusions for α1β1 integrin-mediated fibrosarcoma cell adhesion to [α1(IV)]2α2(IV)434-472 (Eble, J. A., Golbik, R., Mann, K., and Kuhn, K. (1993) EMBO J. 12, 4795-4802). In the present study, we have examined the cell adhesion activities of a third region in type IV collagen. A single-stranded peptide (SSP) incorporating the α1(IV)531-543 sequence promoted the adhesion of melanoma, ovarian carcinoma, and Jurkat cells in a dose-dependent manner, with 40% cell adhesion observed at [SSP] = 1.8, 11.5, and 42.2 μM, respectively. Nearly identical results were obtained for cell adhesion to an all-D-enantiomer of the SSP, suggesting that the cell surface receptor(s) for this site do not discriminate based on chirality. The α1(IV)531-543 sequence maintained its cell adhesion promoting activity when incorporated into a homotrimeric triple-helical polypeptide, although relative levels of adhesion were either slightly enhanced or slightly diminished compared with the SSP. Triple-helical conformation was thus not critical for cellular recognition of the α1(IV)531-543 sequence. Single-site substitution experiments of the SSP showed no overall correlation between the biological effects of substitutions and SSP conformation. The SSP, D-SSP, triple-helical polypeptide, and SSP substitution results suggest that cell recognition of the α1(IV)531-543 sequence is generally independent of substrate conformation. The present and prior studies indicate that 'conformationally dependent' and 'conformationally independent' cellular recognition sites exist within the triple-helical domain of type IV collagen.

AB - Several regions within the triple-helical domain of type IV collagen function as cellular recognition sites. We have demonstrated previously that melanoma cell activities promoted by the α1(IV)1263-1277 sequences are enhanced by triple helicity (Fields, C. G., Mickelson, D. J., Drake, S. L., McCarthy, J. B., and Fields, G. B. (1993) J. Biol. Chem. 268, 14153-14160), whereas Eble et al. reached similar conclusions for α1β1 integrin-mediated fibrosarcoma cell adhesion to [α1(IV)]2α2(IV)434-472 (Eble, J. A., Golbik, R., Mann, K., and Kuhn, K. (1993) EMBO J. 12, 4795-4802). In the present study, we have examined the cell adhesion activities of a third region in type IV collagen. A single-stranded peptide (SSP) incorporating the α1(IV)531-543 sequence promoted the adhesion of melanoma, ovarian carcinoma, and Jurkat cells in a dose-dependent manner, with 40% cell adhesion observed at [SSP] = 1.8, 11.5, and 42.2 μM, respectively. Nearly identical results were obtained for cell adhesion to an all-D-enantiomer of the SSP, suggesting that the cell surface receptor(s) for this site do not discriminate based on chirality. The α1(IV)531-543 sequence maintained its cell adhesion promoting activity when incorporated into a homotrimeric triple-helical polypeptide, although relative levels of adhesion were either slightly enhanced or slightly diminished compared with the SSP. Triple-helical conformation was thus not critical for cellular recognition of the α1(IV)531-543 sequence. Single-site substitution experiments of the SSP showed no overall correlation between the biological effects of substitutions and SSP conformation. The SSP, D-SSP, triple-helical polypeptide, and SSP substitution results suggest that cell recognition of the α1(IV)531-543 sequence is generally independent of substrate conformation. The present and prior studies indicate that 'conformationally dependent' and 'conformationally independent' cellular recognition sites exist within the triple-helical domain of type IV collagen.

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