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Originally published In Press as doi:10.1074/jbc.M409029200 on November 29, 2004

J. Biol. Chem., Vol. 280, Issue 6, 5013-5021, February 11, 2005
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Homotypic Fibrillin-1 Interactions in Microfibril Assembly*

Andrew Marson, Matthew J. Rock, Stuart A. Cain, Lyle J. Freeman, Amanda Morgan, Kieran Mellody, C. Adrian Shuttleworth, Clair Baldock, and Cay M. Kielty{ddagger}

From the Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

We have defined the homotypic interactions of fibrillin-1 to obtain new insights into microfibril assembly. Dose-dependent saturable high affinity binding was demonstrated between N-terminal fragments, between furin processed C-terminal fragments, and between these N- and C-terminal fragments. The N terminus also interacted with a downstream fragment. A post-furin cleavage site C-terminal sequence also interacted with the N terminus, with itself and with the furin-processed fragment. No other homotypic fibrillin-1 interactions were detected. Some terminal homotypic interactions were inhibited by other terminal sequences, and were strongly calcium-dependent. Treatment of an N-terminal fragment with N-ethylmaleimide reduced homotypic binding. Microfibril-associated glycoprotein-1 inhibited N- to C-terminal interactions but not homotypic N-terminal interactions. These fibrillin-1 interactions are likely to regulate pericellular fibrillin-1 microfibril assembly.


Received for publication, August 6, 2004 , and in revised form, October 13, 2004.

* This work was supported by the Medical Research Council (UK), the Biotechnology and Biological Sciences Research Council (UK), European Union Grant QLK6-CT-2001-00332, and a grant from the Royal Society (to C. B.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{ddagger} To whom correspondence should be addressed: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Michael Smith Bldg., Oxford Road, Manchester M13 9PT, United Kingdom. Tel.: 44-161-275-5739; Fax: 44-161-275-5082; E-mail: cay.kielty{at}man.ac.uk.


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