Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/22437
Title: A structural and functional dissection of the cardiac stress response factor MS1.
Authors: Fogl, C
Puckey, L
Hinssen, U
Zaleska, M
El-Mezgueldi, M
Croasdale, R
Bowman, A
Matsukawa, A
Samani, NJ
Savva, R
Pfuhl, M
First Published: 19-Sep-2011
Citation: PROTEINS, 2011
Abstract: MS1 is a protein predominantly expressed in cardiac and skeletal muscle that is upregulated in response to stress and contributes to development of hypertrophy. In the aortic banding model of left ventricular hypertrophy, its cardiac expression was significantly upregulated within 1 h. Its function is postulated to depend on its F-actin binding ability, located to the C-terminal half of the protein, which promotes stabilization of F-actin in the cell thus releasing myocardin-related transcription factors to the nucleus where they stimulate transcription in cooperation with serum response factor. Initial attempts to purify the protein only resulted in heavily degraded samples that showed distinct bands on SDS gels, suggesting the presence of stable domains. Using a combination of combinatorial domain hunting and sequence analysis, a set of potential domains was identified. The C-terminal half of the protein actually contains two independent F-actin binding domains. The most C-terminal fragment (294-375), named actin binding domain 2 (ABD2), is independently folded while a proximal fragment called ABD1 (193-296) binds to F-actin with higher affinity than ABD2 (K(D) 2.21 ± 0.47 μM vs. 10.61 ± 0.7 μM), but is not structured by itself in solution. NMR interaction experiments show that it binds and folds in a cooperative manner to F-actin, justifying the label of domain. The architecture of the MS1 C-terminus suggests that ABD1 alone could completely fulfill the F-actin binding function opening up the intriguing possibility that ABD2, despite its high level of conservation, could have developed other functions. Proteins 2011; © 2011 Wiley Periodicals, Inc.
DOI Link: 10.1002/prot.23201
eISSN: 1097-0134
Links: http://hdl.handle.net/2381/22437
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Biochemistry

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