Marson Andrew, Rock Matthew J, Cain Stuart A, Freeman Lyle J, Morgan Amanda, Mellody Kieran, Shuttleworth C Adrian, Baldock Clair, Kielty Cay M
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
J Biol Chem. 2005 Feb 11;280(6):5013-21. doi: 10.1074/jbc.M409029200. Epub 2004 Nov 29.
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.
我们已对原纤蛋白-1的同型相互作用进行了定义，以便对微原纤维组装有新的认识。在N端片段之间、弗林蛋白酶处理的C端片段之间以及这些N端和C端片段之间均表现出剂量依赖性的饱和高亲和力结合。N端还与一个下游片段相互作用。弗林蛋白酶切割位点C端序列也与N端、自身以及弗林蛋白酶处理的片段相互作用。未检测到原纤蛋白-1的其他同型相互作用。一些末端同型相互作用受到其他末端序列的抑制，且强烈依赖于钙。用N-乙基马来酰亚胺处理N端片段会降低同型结合。微原纤维相关糖蛋白-1抑制N端到C端的相互作用，但不抑制同型N端相互作用。这些原纤蛋白-1的相互作用可能调节细胞周围原纤蛋白-1微原纤维的组装。
