کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1932370 | 1050579 | 2010 | 5 صفحه PDF | دانلود رایگان |
The spectrin-based cytoskeleton is critical for cell stability, membrane organization and membrane protein trafficking. At its core is the high-affinity complex between β-spectrin and ankyrin. Defects in either of these proteins may cause hemolytic disease, developmental disorders, neurologic disease, and cancer. Crystal structures of the minimal recognition motifs of ankyrin and β-spectrin have been determined and distinct recognition mechanisms proposed. One focused on the complementary surface charges of the minimal recognition motifs, whereas the other identified an unusual kink between β-spectrin repeats and suggested a conformation-sensitive binding surface. Using isothermal titration calorimetry and site-directed mutagenesis, we demonstrate the primacy of the inter-repeat kink as the critical determinant underlying spectrin’s ankyrin affinity. The clinical implications of this are discussed in light of recognized linker mutations and polymorphisms in the β-spectrins.
Journal: Biochemical and Biophysical Research Communications - Volume 392, Issue 4, 19 February 2010, Pages 490–494