D-periodic assemblies of type I procollagen

Mould, A. Paul; Hulmes, David J.S.; Holmes, David; Cummings, Christine; Sear, Christopher H. J.; Chapman, John A.

doi:10.1016/0022-2836(90)90267-p

Cited by 32 publications

(16 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, there was no evidence of aggregation in the conditions used, consistent with the known function of the C-propeptide domain in increasing the solubility of the procollagen molecule compared with pN-collagen (procollagen minus the C-propeptide domain) by at least 100-fold (52,53). The value of the diffusion coefficient also gave information on the shape of CPIII in solution.…”

Section: Discussionsupporting

confidence: 68%

Biophysical Characterization of the C-propeptide Trimer from Human Procollagen III Reveals a Tri-lobed Structure

Bernocco¹,

Finet²,

Ebel³

et al. 2001

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Procollagen C-propeptide domains direct chain association during intracellular assembly of procollagen molecules. In addition, they control collagen solubility during extracellular proteolytic processing and fibril formation and interact with cell surface receptors and extracellular matrix components involved in feedback inhibition, mineralization, cell growth arrest, and chemotaxis. At present, three-dimensional structural information for the C-propeptides, which would help to understand the underlying molecular mechanisms, is lacking. Here we have carried out a biophysical study of the recombinant C-propeptide trimer from human procollagen III using laser light scattering, analytical ultracentrifugation, and small angle x-ray scattering. The results show that the trimer is an elongated molecule, which by modeling of the x-ray scattering data appears to be cruciform in shape with three large lobes and one minor lobe. We speculate that each of the major lobes corresponds to one of the three component polypeptide chains, which come together in a junction region to connect to the rest of the procollagen molecule.Fibril-forming collagens (types I, II, III, V, and XI) are synthesized and secreted into the extracellular matrix in precursor form, procollagens (ϳ500 kDa), with large N-and C-terminal propeptide regions (1). The propeptides increase the solubility of the procollagen molecule, thus preventing premature fibril formation inside the cell (2). After secretion, propeptides are cleaved to varying extents by specific procollagen N-and Cproteinases (3-5) and also other proteinases (6, 7), thereby triggering fibril assembly of collagen. Once cleaved, both Nand C-propeptides are thought to control further collagen synthesis by a process of feedback inhibition (8 -11). Also, in the extracellular matrix, the N-propeptides are involved in growth factor signaling (12), whereas the C-propeptides have been implicated in interactions with procollagen C-proteinase enhancer (13), mineralization (14 -16), integrin receptor binding (17, 18), cell growth arrest (19), and chemotaxis (20).In addition to their extracellular roles, numerous observations demonstrate the importance of the C-propeptide domain in chaperone-assisted chain association during intracellular assembly of procollagen molecules (21-24). Each procollagen molecule consists of three polypeptide chains encoded by one or more genes, giving rise to homotrimers or heterotrimers, respectively, with specific chain stoichiometries. For example, procollagen III molecules are homotrimers with the chain composition pro␣1(III) 3 , whereas procollagen I molecules are normally heterotrimers of the form pro␣1(I) 2 pro␣2(I). The C-propeptides direct association within the rough endoplasmic reticulum to ensure correct chain stoichiometry, which is particularly important in cells producing more than one procollagen type. Once associated into a trimer, and after prolyl hydroxylation, triple helix formation within the collagenous region is initiated at the C terminus and proceeds ...

show abstract

Section: Discussionsupporting

confidence: 68%

Biophysical Characterization of the C-propeptide Trimer from Human Procollagen III Reveals a Tri-lobed Structure

Bernocco¹,

Finet²,

Ebel³

et al. 2001

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The results of this body of work are beautifully summarized by Prockop and Hulmes 1994 (Prockop and Hulmes, 1994). Some of the more important results of these investigations demonstrate that : 1) collagen monomers are made soluble by the presence of C- and N-terminal propeptides at relatively high concentrations (up to 1.5 mg/ml in physiological buffer (Mould et al, 1990), 2) fibril diameter depends on the temperature during assembly (Kadler et al, 1990), 3) assembling fibrils possess an inherent polarity (Kadler et al, 1990), 4) assembled fibril morphology is influenced by numerous factors including the momomer concentration (Mould and Hulmes, 1987), pH (Yuan and Veis, 1973), terminal propeptides (Mould et al, 1990), other collagen monomers (Birk et al, 1990; Wenstrup et al, 2004) and proteoglycan core proteins (Brown et al, 2002). In spite of this large body of work investigating factors which control collagen fibril assembly, methods designed to control the organization of the resulting fibrils have received little attention.…”

Section: 0 Stromal Tissue Engineeringmentioning

confidence: 99%

“…This could be accomplished if the cells form stratified layers and secrete large amounts of collagen monomers into the confined space between the organized layers of cells. The most troubling part of this hypothesis is the fact that collagen should form aggregates above 1.5 mg/ml, even with intact propeptides (Mould et al, 1990). Assuming higher concentrations can be stabilized, the direction of the monomeric alignment may be controlled over short distances (and potentially long distances as well) from the cell surface via geometric features or by adhesion complexes.…”

Section: 0 Stromal Tissue Engineeringmentioning

confidence: 99%

Prelude to corneal tissue engineering – Gaining control of collagen organization

Ruberti

Zieske

2008

Progress in Retinal and Eye Research

167

123

View full text Add to dashboard Cite

By most standard engineering practice principles, it is premature to credibly discuss the “engineering” of a human cornea. A professional design engineer would assert that we still do not know what a cornea is (and correctly so), therefore we cannot possibly build one. The proof resides in the fact that there are no clinically viable corneas based on classical tissue engineering methods available. This is possibly because tissue engineering in the classical sense (seeding a degradable scaffolding with a population synthetically active cells) does not produce conditions which support the generation of organized tissue. Alternative approaches to the problem are in their infancy and include the methods which attempt to recapitulate development or to produce corneal stromal analogs de novo which require minimal remodeling. Nonetheless, tissue engineering efforts, which have been focused on producing the fundamental functional component of a cornea (organized alternating arrays of collagen or “lamellae”) may have already provided valuable new insights and tools relevant to development, growth, remodeling and pathologies associated with connective tissue in general. This is because engineers ask a fundamentally different question (How can that be done?) than do biological scientists (How is that done?). The difference in inquiry has prompted us to closely examine (and to mimic) development as well as investigate collagen physicochemical behavior so that we may exert control over organization both in cell-culture (in vitro) and on the benchtop (de novo). Our initial results indicate that reproducing corneal stroma-like local and long-range organization of collagen may be simpler than we anticipated while controlling spacing and fibril morphology remains difficult, but perhaps not impossible in the (reasonably) near term.

show abstract

“…Fleischmajer et al (1988) have also demonstrated that C-propeptides are present at the surface of collagen fibrils during chick embryo skin fibrillogenesis. It is known, too, that, although pCcollagen molecules alone will not self-assemble into fibrils, they will, at a sufficiently high concentration, aggregate into D-periodic tape-like structures (Mould & Hulmes, 1987;Mould et al, 1990). It seems likely therefore that the origins of the enzyme-dependent growth behaviour described here must be sought in terms of some co-assembly of collagen and unprocessed pCcollagen, at an early stage of fibril formation, prior to C-propeptide cleavage by C-proteinase.…”

mentioning

confidence: 99%