Location of Repository

Structure and Function of the Cardiac Stress Response Protein MS1

By Claudia Liliane Fiona Fogl


Myocyte Stress 1 (ms1)/Striated muscle Activator of Rho Signalling (STARS), also known as Actin Binding Rho Activator (ABRA), is a 375 amino acid protein. Its expression increases one hour after the induction of stress in rat hearts through aortic banding. This expression precedes that of early response genes such as c-fos and c-jun. This process has been implicated in the development of left ventricular hypertrophy. ms1/STARS binds to actin, and deletion mutations had shown that residues 234-375 were necessary for actin binding. A mixture of combinatorial domain hunting and rational domain design gave a series of possible domains. Circular dichroism and nuclear magnetic resonance spectroscopy were used to characterise these domains. The first three domains, MSD1 (residues 2-118), MSD2 (40-196) and actin binding domain 1 (ABD1, 193-296) were unfolded, while ABD2 (294-375) was folded. Actin co-sedimentation assays showed that only ABD1 and ABD2 bound to actin. They bound to actin independently. The structure of ABD2 was determined using NMR. Mutation studies, based on the NMR structure and on data about the conservation of positively-charged regions in ms1/STARS homologues, were used to identify the actin binding surface of ABD2. The structure of ABD2 was shown to be a winged helix-turn-helix domain. These domains are often DNA binding domains. When DNA binding was attempted, it was shown that ABD1, ABD2 and the tandem of ABD1 and ABD2 bound to DNA. The identification of the actin binding domain and the discovery of a novel DNA binding ability open up many more possible functions of ms1/STARS

Publisher: University of Leicester
Year: 2011
OAI identifier: oai:lra.le.ac.uk:2381/9408

Suggested articles



  1. (2003). Actin binding proteins: regulation of cytoskeletal microfilaments” doi
  2. (2003). Actin dynamics control SRF activity by regulation of its coactivator MAL” doi
  3. (2006). Actin homolog MreBH governs cell morphogenesis by localization of the cell wall hydrolase LytE” doi
  4. (2001). Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor” doi
  5. (2003). Bacterial mitosis: ParM of plasmid R1 moves plasmid DNA by an actin-like insertional polymerisation mechanism” Mol Cell
  6. (2003). Calcium/calmodulin-dependent kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy” doi
  7. (2000). Cardiac tissue enriched factors serum response factor and GATA-4 are mutual coregulators” doi
  8. (2008). Comparative in silico analysis identifies bona fide MyoD binding sites within the Myocyte Stress 1 gene promoter” doi
  9. (2001). Control of Cell Shape in Bacteria: heleical, actin-like filaments in Bacillus subtilis” doi
  10. (1992). Escherichia coli biotin holoenzyme synthetase/bio repressor crystal structure delineates the biotin- and DNA-binding domains” doi
  11. (1990). Folding transition in the DNA-binding domain of GCN4 on specific binding to DNA” doi
  12. (2006). Hunting: An effective approach for the identification of soluble protein domains adaptable to high-throughput applications” doi
  13. (2005). Kruppel-like factor 4 abrogates myocardin-induced activation of smooth muscle gene expression” doi
  14. (1982). Model-free approach to the interpretation of nuclear magneticresonance relaxation in macromolecules. 1. Theory and range of validity” doi
  15. (2007). Modulation of adverse cardiac remodelling by STARS, a mediator of MEF2 signalling and SRF activity” doi
  16. (2005). Myocardin-related transcription factor B is required in cardiac neural crest for smooth muscle differentiation and cardiovascular development” doi
  17. (2005). RONN: the bio-basis function neural network technique applied to the detection of natively disordered regions in proteins” doi
  18. (1996). serum response factor expression restricted primarily to muscle cell lineages is required for alpha-actin gene transcription” doi
  19. (1998). Smooth muscle differentiation marker gene expression is regulated by RhoA-mediated actin polymerisation” doi
  20. (2006). Stabilization of a binary protein complex by intein-mediated cyclization”
  21. (2004). ternary complex factors compete for SRF to control smooth muscle gene expression” doi
  22. (2002). The CCPN project: An Interim Report on a data model for the NMR community” doi
  23. (2001). The crystal structure of MarR, a regulator of multiple antibiotic resistance, at 2.3 Å resolution” doi
  24. (1994). The LIM domain is a modular protein-binding interface” doi
  25. (1996). The Ras GTPase-activating-protein-related human protein IQGAP2 harbours a potential actin binding domain and interacts with calmodulin and Rho family GTPases” doi
  26. (1997). Torsion Angle Dynamics for NMR Structure Calculation with the New Program DYANA” doi

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.