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Functional analysis of an ADAMTS10 signal peptide mutation in Weill-Marchesani syndrome demonstrates a long-range effect on secretion of the full-length enzyme by Wendy E. Kutz; Lauren W. Wang; Nathalie Dagoneau; Kazimir J. Odrcic; Valerie Cormier-Daire; Elias I. Traboulsi; Suneel S. Apte is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Functional analysis of an ADAMTS10 signal peptide mutation in Weill-Marchesani syndrome demonstrates a long-range effect on secretion of the full-length enzyme about?
We report the identification and functional analysis of the first missense ADAMTS10 mutation (c.73G4A; p.Ala25Thr) causing recessive Weill-Marchesani syndrome (WMS). The Ala25 residue affected by the missense mutation is at the À1 position relative to the ADAMTS10 signal peptidase cleavage site. p.Ala25Thr substituted full-length ADAMTS10 showed consistent and significantly diminished secretion in both HEK293F and Cos-1 cells. However, a C-terminally truncated construct lacking the ancillary domain and containing only the signal peptide, the propeptide and the catalytic domain (p.Ala25Thr Pro-Cat) was efficiently secreted in both HEK293F cells and Cos-1 cells. Edman degradation of purified p.Ala25Thr Pro-Cat and p.Ala25Thr substituted full-length ADAMTS10 from HEK293F cells demonstrated correct signal peptide processing. Thus, the p.Ala25Thr substitution hinders secretion of full-length ADAMTS10, but not Pro-Cat from cells, yet permits signal peptide removal. We infer that folding of the complex C-terminal ancillary domain is the ratelimiting step in biosynthesis of ADAMTS10, and that it (but not Pro-Cat) is sensitive to subtle changes in efficiency of signal peptide cleavage. Thes
Who reads Functional analysis of an ADAMTS10 signal peptide mutation in Weill-Marchesani syndrome demonstrates a long-range effect on secretion of the full-length enzyme?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Wendy E. Kutz; Lauren W. Wang; Nathalie Dagoneau; Kazimir J. Odrcic; Valerie Cormier-Daire; Elias I. Traboulsi; Suneel S. Apte
- Publisher
- Hindawi Limited
- Published
- 2008
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)