Author: Reinhardt D.
Publisher: Oxford University Press
ISSN: 1460-2083
Source: Human Molecular Genetics, Vol.7, Iss.13, 1998-12, pp. : 2039-2044
Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.
Abstract
Fibrillin-1 is a major component of the 10 nm microfibrils of the extracellular matrix (ECM). It is synthesized as an ∼350 kDa precursor molecule, profibrillin-1, which is proteolytically processed into its biologically active ∼320 kDa form. Furin, a calcium-dependent endoprotease of the subtilisin family, which is known to be the processing enzyme for a variety of proproteins, is believed to be responsible for the N-terminal proteolytic cleavage of profibrillin-1. In this article we provide several lines of evidence that the C-terminal trimming of profibrillin-1 also occurs via a furin-type activity. Edman degradation of a small recombinant C-terminal subdomain of fibrillin-1 revealed complete processing of the peptide immediately after the tribasic recognition sequence (R-X-K/R-R) for furin. In vitro expression experiments using another recombinant construct consisting of the C-terminal half of fibrillin-1 indicated that disruption of the putative recognition sequence for furin by site-directed mutagenesis drastically impairs proteolytic processing of the propeptide. In addition, our results suggest that the N-terminal half of fibrillin-1 is necessary for its incorporation into the ECM.
Related content
By Sim Chou Hung Lio Daisy Sio Seng Mok Su San Masters Colin L. Hill Andrew F. Culvenor Janetta G. Cheng Heung-Chin
Human Molecular Genetics, Vol. 15, Iss. 21, 2006-11 ,pp. :
Human Molecular Genetics, Vol. 14, Iss. 10, 2005-05 ,pp. :
By Müller C.R.
Human Molecular Genetics, Vol. 10, Iss. 25, 2001-12 ,pp. :