The regulation of size and form in the assembly of collagen fibrils in vivo

Chapman, John A.

doi:10.1002/bip.360280803

Cited by 83 publications

(34 citation statements)

References 82 publications

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“…This is in agreement with in vivo studies, where intermediates are identified as being 8 nm in diameter when dehydrated (9) or 11 nm when hydrated (10), assuming continued assembly from two 4-nm microfibrils.…”

supporting

confidence: 91%

COMP Acts as a Catalyst in Collagen Fibrillogenesis

Halász

Kassner²,

Mörgelin

et al. 2007

Journal of Biological Chemistry

271

220

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We have previously reported that COMP (cartilage oligomeric matrix protein) is prominent in cartilage but is also present in tendon and binds to collagens I and II with high affinity. Here we show that COMP influences the fibril formation of these collagens. Fibril formation in the presence of pentameric COMP was much faster, and the amount of collagen in fibrillar form was markedly increased. Monomeric COMP, lacking the N-terminal coiled-coil linker domain, decelerated fibrillogenesis. The data show that stimulation of collagen fibrillogenesis depends on the pentameric nature of COMP and not only on collagen binding. COMP interacts primarily with free collagen I and II molecules, bringing several molecules to close proximity, apparently promoting further assembly. These assemblies further join in discrete steps to a narrow distribution of completed fibril diameters of 149 ؎ 16 nm with a banding pattern of 67 nm. COMP is not found associated with the mature fibril and dissociates from the collagen molecules or their early assemblies. However, a few COMP molecules are found bound to more loosely associated molecules at the tip/end of the growing fibril. Thus, COMP appears to catalyze the fibril formation by promoting early association of collagen molecules leading to increased rate of fibrillogenesis and more distinct organization of the fibrils.

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supporting

confidence: 91%

COMP Acts as a Catalyst in Collagen Fibrillogenesis

Halász

Kassner²,

Mörgelin

et al. 2007

Journal of Biological Chemistry

271

220

View full text Add to dashboard Cite

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“…The mean intermolecular spacing in collagen fibrils of uncompressed human cartilage can be estimated as 1.865 nm from measurements of the equatorial x-ray scattering (16). If the number of triple-helical domains in a transverse section through the fibril ϭ N, then the diameter (D eff nm) of the fibril is then given by: D eff ϭ 1.96͌N nm (28).…”

Section: Calculation Of Effective Hydrated Diameter For Model Fibrilmentioning

confidence: 99%

The 10+4 microfibril structure of thin cartilage fibrils

Holmes

Kadler

2006

Proc. Natl. Acad. Sci. U.S.A.

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Determining the structure of cartilage collagen fibrils will provide insights into how mutations in collagen genes affect cartilage formation during skeletal morphogenesis and understanding the mechanism of fibril growth. The fibrils are indeterminate in size, heteropolymeric, and highly cross-linked, which make them refractory to analysis by conventional high-resolution structure determination techniques. Electron microscopy has been limited to making simple measurements of fibril diameter and immunolocalizing certain molecules at the fibril surface. Consequently, structural information on the fibrils is limited. In this study we have used scanning transmission electron microscopic mass mapping, analysis of axial stain exclusion pattern, and r-weighted back-projection techniques to determine the intermediate resolution (to Ϸ4 nm) structure of thin collagen fibrils from embryonic cartilage. The analyses show that the fibrils are constructed from a 10؉4 microfibrillar arrangement in which a core of four microfibrils is surrounded by a ring of 10 microfibrils. Accurate mass measurements predict that each microfibril contains five collagen molecules in cross-section. Based on the proportion of collagen II, IX, and XI in the fibrils, the fibril core comprises two microfibrils each of collagen II and collagen XI. Single molecules of collagen IX presumably occur at the fibril surface between the extended N-terminal domains of collagen XI. The 10؉4 microfibril structure explains the mechanism of diameter limitation in the narrow fibrils and the absence of narrow collagen fibrils in cartilage lacking collagen XI.chondrodysplasia ͉ collagen ͉ electron microscopy ͉ mass mapping ͉ reconstruction T he ability of cartilage to withstand cycles of compression and relaxation relies on a felt-like extracellular matrix (ECM) of insoluble collagen fibrils within a concentrated solution of proteoglycans and glycoconjugates. The collagen fibrils withstand the swelling pressure exerted on the ECM by the hydrated glycosaminoglycan side chains of the proteoglycans. However, this apparently simple role of the collagen fibrils belies enormous effort over many years to understand fibril structure and function as a means of explaining how mutations in cartilage fibril genes produce developmental defects. In particular, it is perplexing why cartilage has two distinct populations of collagen fibrils; one thin (Ϸ20-nm diameter) and the other thick (Ϸ40-nm diameter). Also, it is a quandary why cartilage fibrils of diameter between 20 and 40 nm do not exist in cartilage; also whereas the thin fibrils are all Ϸ20 nm in diameter, the thick fibrils have a much broader diameter distribution. In this respect, the thick fibrils are more like fibrils in noncartilagenous tissues, which can range from 30 to 500 nm in diameter (1). We reasoned that determination of the structure of the thin fibrils was an essential first step in understanding cartilage fibril structure and function.Cartilage fibrils are D-periodic (where D Ϸ 67 nm), indeterminate in leng...

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“…1). The N-propeptide has been proposed to inhibit collagen synthesis (17,18) and regulate the diameter of collagen fibrils by inhibiting the lateral growth during fibrillogenesis (19). The N-propeptide of type II procollagen has recently been shown to bind TGF-␤1 and bone morphogenetic protein-2 (BMP-2) and has been proposed to play a role in the extracellular matrix deposition of BMPs in chondrogenic tissue (20).…”

Section: Thrombospondin 1 (Tsp1)mentioning

confidence: 99%

Physical Characterization of the Procollagen Module of Human Thrombospondin 1 Expressed in Insect Cells

Misenheimer

Huwiler

Annis

et al. 2000

Journal of Biological Chemistry

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Thrombospondin 1 (TSP1) is a homotrimeric glycoprotein composed of 150-kDa subunits connected by disulfide bridges. The procollagen module of thrombospondin 1 has been implicated in antiangiogenic activity. Procollagen modules are found in a number of extracellular proteins and are identifiable by 10 cysteines with characteristic spacing. We expressed and studied the procollagen module (C) of human TSP1, both by itself and in the context of the adjoining oligomerization sequence (o) and N-terminal module (N). The coding sequences were introduced into baculoviruses along with an N-terminal signal sequence and C-terminal polyhistidine tag. Proteins were purified from conditioned medium of infected insect cells by nickel-chelate chromatography. NoC is a disulfide bonded trimer and cleaves readily at a site of preferential proteolysis to yield monomeric N and trimeric oC. These are known properties of full-length TSP1. Mass spectroscopy indicated that C is N-glycosylated, and all 10 cysteine residues of C are in disulfides. By equilibrium ultracentrifugation, C is a monomer in physiological salt solution. Circular dichroism, intrinsic fluorescence, and differential scanning calorimetry experiments suggest that the stability of C is determined by the disulfides. The two tryptophans of C are in a polar, exposed environment as assessed by iodide fluorescence quenching and solvent perturbation. The oC far UV circular dichroism spectrum could be modeled as the sum of C and a coiled-coil oligomerization domain. The results indicate that the recombinant C folds autonomously into its native structure, and trimerization of the modules in TSP1 does not perturb their structures.

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The regulation of size and form in the assembly of collagen fibrils in vivo

Cited by 83 publications

References 82 publications

COMP Acts as a Catalyst in Collagen Fibrillogenesis

COMP Acts as a Catalyst in Collagen Fibrillogenesis

The 10+4 microfibril structure of thin cartilage fibrils

Physical Characterization of the Procollagen Module of Human Thrombospondin 1 Expressed in Insect Cells

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