Structural cooperativity in spectrin type repeats motifs of dystrophin

被引:17
作者
Saadat, Laleh [1 ]
Pittman, Lena [1 ]
Menhart, Nick [1 ]
机构
[1] IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2006年 / 1764卷 / 05期
关键词
dystrophin; spectrin-type-repeat; stability; domain; unfolding;
D O I
10.1016/j.bbapap.2006.02.012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Dystrophin is a member of the spectrin family of proteins, which are characterized as being predominantly composed the spectrin-type-repeat, a triple a-helical bundle motif present in multiple tandem copies, producing a rod-like shape. Whether or not this motif, which is determined by sequence homology, is correlated with biophysical domains in the intact protein is uncertain. The nature of the domain structure impacts the flexibility and shape of the rod region of this protein, which is a target for modification in several therapeutic approaches aimed at Duchenne Muscular Dystrophy, a common and fatal genetic disease caused by defective dystrophin. We examined three such motifs in dystrophin, expressing them recombinantly both singly and in tandem, and studying their thermodynamic properties by solvent and thermal denaturation. We have found that the degree to which they are independently stable and expressible varies considerably. The fourth motif appears to be largely stable and independent, whereas the third and second motifs interact strongly. (c) 2006 Elsevier B.V. All rights reserved.
引用
收藏
页码:943 / 954
页数:12
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