The NH(2)-terminal propeptides of fibrillar collagens: highly conserved domains with poorly understood functions. |
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Authors: | Paul Bornstein |
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Affiliation: | Department of Biochemistry, University of Washington, WA, Seattle 98195, USA. bornstein@u.washington.edu |
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Abstract: | The impetus for this review comes from the recent finding that the absence of the majority of the non-triple-helical sequence in the NH(2)-terminal propeptide (N-propeptide) of the pro alpha 1(I) collagen chain fails to generate a significant phenotype in the mouse (Bornstein et al., J. Biol. Chem., 277:2605-2613, 2002). This result is in apparent conflict with those of numerous studies in vitro that have implicated the N-propeptide in a number of processes that are involved in the biogenesis, maturation and function of type 1 collagen. To seek an explanation for this discrepancy, the sequences of the highly conserved, 55-57-amino acid, cysteine-rich repeats (CRR), which constitute the majority of the globular domains in the N-propeptides, were compared among 13 vertebrate species. Surprisingly, the CRR in mice and rats differs substantially from those in other mammalian species. Indeed, the CRR in birds, fish and amphibia are more similar to those of other mammals than are the CRR in rodents. This finding raises the possibility that the mutant mouse, which lacks exon 2 that encodes the CRR in the N-propeptide, might not be an appropriate model in which to study the function of the N-propeptide in other mammals. Alternatively, compensation, possibly by procollagens II or III, could account for the mild phenotype of the exon 2-deleted mouse. Yet another possibility is that the CRR plays a developmental role in the mouse, akin to that recently proposed for the N-propeptide in type IIA procollagen, rather than a function in collagen biogenesis. Some support for the latter possibility is provided by the observation that, on one background, the breeding of heterozygous exon 2-deleted mice generated homozygous mutants at less than the expected frequency. Experiments to examine these possibilities are proposed. |
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