The molecular structure of human tissue type XV presents a unique conformation among the collagens

Jeanne C. Myers, Peter S. Amenta, Arnold S. Dion, Justin P. Sciancalepore, Chandrasekaran Nagaswami, John W. Weisel, Peter D. Yurchenco

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Establishing the structure of the non-fibrillar collagens has provided a unique perspective to understanding their specialized functions in the extracellular matrix. These proteins exhibit very diverse conformations and supramolecular assemblies. Type XV collagen is a large macromolecule distinguished by a highly interrupted collagenous domain and many utilized sites of attachment for CS (chondroitin sulfate) and HS (heparan sulfate) glycosaminoglycan chains. It is present in most basement membrane zones of human tissues, where it is found closely associated with large collagen fibrils. To determine the molecular shape and organization of type XV, the protein was purified from human umbilical cords by salt extraction, and by ion-exchange and antibody-affinity chromatography. The representation of type XV in one of its most abundant tissue sources is estimated at only (1-2) × 10-4 % of dry weight. The molecules examined by transmission electron microscopy after rotary shadowing were visualized in multiple forms. Relatively few type XV monomers appeared elongated and kinked; most molecules were found in a knot/figure-of-eight/pretzel configuration not previously described for a collagen. Collective measurements of these populations revealed an average length of 193 ± 16 nm. At the N-terminal end, identified by C-terminal antibody binding, were three 7.7 nm-diameter spheres, corresponding to TSPN-1 (N-terminal module of thrombospondin-1) modules, and attached to the collagen backbone by a short linker. The type XV monomers show the ability to self-assemble into higher-order structures. Some were arranged in complex clusters, but simpler oligomers, which may represent intermediates, were observed in a cruciform pattern with intermolecular binding sites that probably originate in the interruption sequences. The morphology of type XV is thus the antithesis of the fibrillar collagens, and the shape attains the required flexibility to form the spectrum of interconnecting links between banded fibrils at the basement membrane/interstitial border. These type XV structures may act as a biological 'spring' to stabilize and enhance resilience to compressive and expansive forces, and the multimers, in particular, with selective complements of many localized CS and HS chains, may be instrumental in spatial and temporal recruitment of modulators in growth, development and pathological processes.

Original languageEnglish (US)
Pages (from-to)535-544
Number of pages10
JournalBiochemical Journal
Volume404
Issue number3
DOIs
StatePublished - Jun 15 2007

Fingerprint

Molecular Structure
Molecular structure
Conformations
Collagen
Tissue
Heparitin Sulfate
Chondroitin Sulfates
Basement Membrane
Non-Fibrillar Collagens
Monomers
Fibrillar Collagens
Thrombospondin 1
Affinity chromatography
Molecules
Antibody Affinity
Antibodies
Umbilical Cord
Ion Exchange
Pathologic Processes
Glycosaminoglycans

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Keywords

  • Basement membrane
  • Chondroitin sulfate
  • Extracellular matrix
  • Heparan sulfate
  • Proteoglycan
  • Rotary shadowing
  • Type XV collagen

Cite this

Myers, J. C., Amenta, P. S., Dion, A. S., Sciancalepore, J. P., Nagaswami, C., Weisel, J. W., & Yurchenco, P. D. (2007). The molecular structure of human tissue type XV presents a unique conformation among the collagens. Biochemical Journal, 404(3), 535-544. https://doi.org/10.1042/BJ20070201
Myers, Jeanne C. ; Amenta, Peter S. ; Dion, Arnold S. ; Sciancalepore, Justin P. ; Nagaswami, Chandrasekaran ; Weisel, John W. ; Yurchenco, Peter D. / The molecular structure of human tissue type XV presents a unique conformation among the collagens. In: Biochemical Journal. 2007 ; Vol. 404, No. 3. pp. 535-544.
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abstract = "Establishing the structure of the non-fibrillar collagens has provided a unique perspective to understanding their specialized functions in the extracellular matrix. These proteins exhibit very diverse conformations and supramolecular assemblies. Type XV collagen is a large macromolecule distinguished by a highly interrupted collagenous domain and many utilized sites of attachment for CS (chondroitin sulfate) and HS (heparan sulfate) glycosaminoglycan chains. It is present in most basement membrane zones of human tissues, where it is found closely associated with large collagen fibrils. To determine the molecular shape and organization of type XV, the protein was purified from human umbilical cords by salt extraction, and by ion-exchange and antibody-affinity chromatography. The representation of type XV in one of its most abundant tissue sources is estimated at only (1-2) × 10-4 {\%} of dry weight. The molecules examined by transmission electron microscopy after rotary shadowing were visualized in multiple forms. Relatively few type XV monomers appeared elongated and kinked; most molecules were found in a knot/figure-of-eight/pretzel configuration not previously described for a collagen. Collective measurements of these populations revealed an average length of 193 ± 16 nm. At the N-terminal end, identified by C-terminal antibody binding, were three 7.7 nm-diameter spheres, corresponding to TSPN-1 (N-terminal module of thrombospondin-1) modules, and attached to the collagen backbone by a short linker. The type XV monomers show the ability to self-assemble into higher-order structures. Some were arranged in complex clusters, but simpler oligomers, which may represent intermediates, were observed in a cruciform pattern with intermolecular binding sites that probably originate in the interruption sequences. The morphology of type XV is thus the antithesis of the fibrillar collagens, and the shape attains the required flexibility to form the spectrum of interconnecting links between banded fibrils at the basement membrane/interstitial border. These type XV structures may act as a biological 'spring' to stabilize and enhance resilience to compressive and expansive forces, and the multimers, in particular, with selective complements of many localized CS and HS chains, may be instrumental in spatial and temporal recruitment of modulators in growth, development and pathological processes.",
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Myers, JC, Amenta, PS, Dion, AS, Sciancalepore, JP, Nagaswami, C, Weisel, JW & Yurchenco, PD 2007, 'The molecular structure of human tissue type XV presents a unique conformation among the collagens', Biochemical Journal, vol. 404, no. 3, pp. 535-544. https://doi.org/10.1042/BJ20070201

The molecular structure of human tissue type XV presents a unique conformation among the collagens. / Myers, Jeanne C.; Amenta, Peter S.; Dion, Arnold S.; Sciancalepore, Justin P.; Nagaswami, Chandrasekaran; Weisel, John W.; Yurchenco, Peter D.

In: Biochemical Journal, Vol. 404, No. 3, 15.06.2007, p. 535-544.

Research output: Contribution to journalArticle

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AU - Myers, Jeanne C.

AU - Amenta, Peter S.

AU - Dion, Arnold S.

AU - Sciancalepore, Justin P.

AU - Nagaswami, Chandrasekaran

AU - Weisel, John W.

AU - Yurchenco, Peter D.

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Y1 - 2007/6/15

N2 - Establishing the structure of the non-fibrillar collagens has provided a unique perspective to understanding their specialized functions in the extracellular matrix. These proteins exhibit very diverse conformations and supramolecular assemblies. Type XV collagen is a large macromolecule distinguished by a highly interrupted collagenous domain and many utilized sites of attachment for CS (chondroitin sulfate) and HS (heparan sulfate) glycosaminoglycan chains. It is present in most basement membrane zones of human tissues, where it is found closely associated with large collagen fibrils. To determine the molecular shape and organization of type XV, the protein was purified from human umbilical cords by salt extraction, and by ion-exchange and antibody-affinity chromatography. The representation of type XV in one of its most abundant tissue sources is estimated at only (1-2) × 10-4 % of dry weight. The molecules examined by transmission electron microscopy after rotary shadowing were visualized in multiple forms. Relatively few type XV monomers appeared elongated and kinked; most molecules were found in a knot/figure-of-eight/pretzel configuration not previously described for a collagen. Collective measurements of these populations revealed an average length of 193 ± 16 nm. At the N-terminal end, identified by C-terminal antibody binding, were three 7.7 nm-diameter spheres, corresponding to TSPN-1 (N-terminal module of thrombospondin-1) modules, and attached to the collagen backbone by a short linker. The type XV monomers show the ability to self-assemble into higher-order structures. Some were arranged in complex clusters, but simpler oligomers, which may represent intermediates, were observed in a cruciform pattern with intermolecular binding sites that probably originate in the interruption sequences. The morphology of type XV is thus the antithesis of the fibrillar collagens, and the shape attains the required flexibility to form the spectrum of interconnecting links between banded fibrils at the basement membrane/interstitial border. These type XV structures may act as a biological 'spring' to stabilize and enhance resilience to compressive and expansive forces, and the multimers, in particular, with selective complements of many localized CS and HS chains, may be instrumental in spatial and temporal recruitment of modulators in growth, development and pathological processes.

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KW - Basement membrane

KW - Chondroitin sulfate

KW - Extracellular matrix

KW - Heparan sulfate

KW - Proteoglycan

KW - Rotary shadowing

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Myers JC, Amenta PS, Dion AS, Sciancalepore JP, Nagaswami C, Weisel JW et al. The molecular structure of human tissue type XV presents a unique conformation among the collagens. Biochemical Journal. 2007 Jun 15;404(3):535-544. https://doi.org/10.1042/BJ20070201