Mosaic structure of globular domains in the human type VI collagen alpha 3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and aprotinin type protease inhibitors.

Chu, Mon‐Li; Zhang, R.Z.; Pan, Te‐Cheng; Stokes, David G.; Conway, D.; Kuo, Huey‐Ju; Glanville, Robert W.; Mayer, Ulríke; Mann, Karlheinz; Deutzmann, Rainer

doi:10.1002/j.1460-2075.1990.tb08122.x

Cited by 187 publications

(116 citation statements)

References 55 publications

(35 reference statements)

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“…Total RNA was isolated from confluent fibroblasts with an RNeasy kit (Qiagen). The probes for Northern blots were a mixture of [ 32 P]dCTP-labeled cDNA clones (F157, F225, and FO19) encoding the three collagen VI chains (19,20). Hybridization signals were detected with a PhosphorImager and quantified with the ImageQuant software (Amersham Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

Zhang

Sabatelli

Pan

et al. 2002

Journal of Biological Chemistry

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We recently reported a severe deficiency in collagen type VI, resulting from recessive mutations of the COL6A2 gene, in patients with Ullrich congenital muscular dystrophy. Their parents, who are all carriers of one mutant allele, are unaffected, although heterozygous mutations in collagen VI caused Bethlem myopathy. Here we investigated the consequences of three COL6A2 mutations in fibroblasts from patients and their parents in two Ullrich families. All three mutations lead to nonsense-mediated mRNA decay. However, very low levels of undegraded mutant mRNA remained in patient B with compound heterozygous mutations at the distal part of the triple-helical domain, resulting in deposition of abnormal microfibrils that cannot form extensive networks. This observation suggests that the C-terminal globular domain is not essential for triple-helix formation but is critical for microfibrillar assembly. In all parents, the COL6A2 mRNA levels are reduced to 57-73% of the control, but long term collagen VI matrix depositions are comparable with that of the control. The almost complete absence of abnormal protein and nearnormal accumulation of microfibrils in the parents may account for their lack of myopathic symptoms.Congenital atonic-sclerotic muscular dystrophy (MIM 254090), first described by Ullrich in 1930 (1) and later referred to as Ullrich syndrome, delineates a distinct subtype of congenital muscular dystrophy, characterized by muscle weakness and hypotonia starting at birth or in early infancy (2). The salient clinical features of Ullrich congenital muscular dystrophy (UCMD) 1 are multiple joint contractures associated with distal hyperextensibility. Patients frequently display additional skeletal deformities, including scoliosis and kyphosis, and suffer from respiratory difficulties early in life. The mode of inheritance is consistent with an autosomal recessive pattern (3). We and others (4 -6) have recently shown that a deficiency in collagen type VI, resulting from homozygous or compound heterozygous mutations in COL6A2, which encodes one of the three collagen VI chains, causes UCMD. Subsequently, three homozygous mutations in another collagen VI gene, COL6A3, have been shown to cause severe and mild forms of UCMD with complete or partial deficiency in collagen VI (7).Several distinctive clinical features of UCMD are also observed in Bethlem myopathy, a mild, dominantly inherited congenital disorder characterized by muscle wasting and multiple joint contractures (8). Missense and splicing mutations in all three collagen VI genes have been reported in patients with Bethlem myopathy (9 -12). In addition, functional haploinsufficiency of the COL6A1 gene has been demonstrated in three Bethlem myopathy patients (13-15). All the known mutations show a high penetrance. Recently, in three families the dominant limb-girdle muscular dystrophy has also been shown to be caused by missense mutations in the COL6A1 and COL6A2 genes (16). Thus, abnormalities in collagen VI can lead to a wide spectrum of clinical phenotypes...

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Section: Methodsmentioning

confidence: 99%

Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

Zhang

Sabatelli

Pan

et al. 2002

Journal of Biological Chemistry

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“…Often the biological significance is unknown, but in several cases the alternatively spliced regions were postulated to be important for the interaction with other extracellular matrix components as in elastin (Pollock et a., 1990), type IX collagen (Svoboda et a!., 1988), or type VI collagen (Chu et a., 1989(Chu et a., , 1990). In the case of type VI collagen, experimental evidence was presented for the interaction of its so-called A-domains with collagen type I (Bonaldo et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.

et al. 1991

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In the chicken, three tenascin variants have been characterized that are generated by alternative splicing of 3 of its 11 fibronectin type III repeats. Using monoclonal antibodies that react with common regions versus extra repeats of tenascin, we could distinguish and separate tenascin variants and investigate their interaction with fibronectin using multiple experimental procedures. Interestingly, in all assays used the smallest tenascin variant bound more strongly to fibronectin than the larger ones. These biochemical data were paralleled by the observation that in chick embryo fibroblast cultures only the smallest form of tenascin could be detected in the fibronectin-rich extracellular matrix network laid down by the cells. Furthermore, each tissue present in adult chicken gizzard contained a distinct set of tenascin variants. Those tissues particularly rich in extracellular matrix, such as the tendon, contained the smallest tenascin only. Intermediate-sized tenascin was present in smooth muscle, whereas the largest form was exclusively detectable underneath the epithelial lining of the villi. Thus it appears that cell type-specific forms of tenascin exist that are appropriate for the functional requirements of the respective extracellular matrices.

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“…Two Kunitz-type inhibitor domains have been identified as parts of inter-a-trypsin inhibitor (Hochstrasser and Wachter, 1979). Tissue factor pathway inhibitor contains three domains (Wun et al, 1988), while Alzheimer's amyloid /I-protein precursor (Kitaguchi et al, 1988;Ponte et al, 1988;Tanzi et al, 1988) and collagen type VI (Chu et al, 1990) each contains a single Kunitz domain.…”

mentioning

confidence: 99%

Binding of bovine pancreatic trypsin inhibitor to heparin binding protein/CAP37/azurocidin

Petersen

Birktoft

Flodgaard

1993

European Journal of Biochemistry

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Heparin-binding protein (HBP; also known as CAP37 or azurocidin) is a member of the serine proteinase family. Evolution, however, has reverted this protein into a non-proteolytic form by mutation of two of the three residues of the active-site triad. Although proteolytically inactive, the human heparin-binding protein (hHBP) is still capable of binding bovine pancreatic trypsin inhibitor (BPTI). This was demonstrated by affinity chromatography to BPTI immobilized on a solid matrix and by studies on plasmin inhibition kinetics. hHBP competes with plasmin for BPTI and this effect on plasmin inhibition has been analyzed in terms of a kinetic model. A dissociation constant, Kd = 0.1 pM, was found for the interaction between BPTI and hHBP. The hHBP provides an example of a serine proteinase which has lost its catalytic function by reverting residues of the active center while still preserving its capability of specific interactions with Kunitz inhibitors. pHBP, the porcine counterpart to hHBP, on the other hand, was incapable of BPTI binding. The structural basis for the BPTI binding to the human protein and the species difference is discussed in terms of putative three-dimensional structures of the proteins derived by comparative molecular modelling methods.

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Mosaic structure of globular domains in the human type VI collagen alpha 3 chain: similarity to von Willebrand factor, fibronectin, actin, salivary proteins and aprotinin type protease inhibitors.

Cited by 187 publications

References 55 publications

Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

Tenascin variants: differential binding to fibronectin and distinct distribution in cell cultures and tissues.

Binding of bovine pancreatic trypsin inhibitor to heparin binding protein/CAP37/azurocidin

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