Fesselin and caldesmon: natively unfolded proteins in smooth muscle regulation
Dysregulation of smooth muscle contraction is linked to diseases such as atherosclerosis, asthma, hypertension, urinary incontinence, premature birth and others. The goal of this project is to contribute to our understanding of the mechanisms of smooth muscle regulation. Caldesmon and fesselin are actin-binding proteins abundant in smooth muscle that have multiple binding partners and are well positioned to alter smooth muscle contraction. Because fesselin is a heat-stable proline rich protein that has many properties in common with the natively unfolded COOH terminal fragment of caldesmon, we sought to determine whether fesselin is natively unfolded. We compared fesselin to a known globular protein (myosin S1) and the unfolded C-terminal 22 kDa fragment of caldesmon (CaD22) using techniques such as gel filtration, intrinsic tryptophan fluorescence and circular dichroism. We showed that fesselin is a natively unfolded protein. We also investigated the effects of phosphorylation by p21-activated kinase 3, PAK, and calmodulin on CaD22. We found a novel regulatory region between the residues 627-642 in the unfolded caldesmon C-terminus and identified four minor residues slowly phosphorylated by PAK. Phosphorylation of this region alters both the ability of caldesmon to inhibit actomyosin ATPase and the interactions between caldesmon and Ca2+-calmodulin that may contribute to the overall regulation of caldesmon's activity.
Hamden, Svetlana. (January 2010). Fesselin and caldesmon: natively unfolded proteins in smooth muscle regulation (Doctoral Dissertation, East Carolina University). Retrieved from the Scholarship. (http://hdl.handle.net/10342/2927.)
Hamden, Svetlana. Fesselin and caldesmon: natively unfolded proteins in smooth muscle regulation. Doctoral Dissertation. East Carolina University, January 2010. The Scholarship. http://hdl.handle.net/10342/2927. February 21, 2019.
Hamden, Svetlana, “Fesselin and caldesmon: natively unfolded proteins in smooth muscle regulation” (Doctoral Dissertation., East Carolina University, January 2010).
Hamden, Svetlana. Fesselin and caldesmon: natively unfolded proteins in smooth muscle regulation [Doctoral Dissertation]. Greenville, NC: East Carolina University; January 2010.
East Carolina University