%0 Journal Article
%T Human Tonic and Phasic Smooth Muscle Myosin Isoforms Are Unresponsive to the Loop 1 Insert
%A Katalin Ajtai
%A Azad Mayanglambam
%A Yihua Wang
%A Thomas P. Burghardt
%J ISRN Structural Biology
%D 2013
%R 10.1155/2013/634341
%X Smooth muscle myosin gene products include two isoforms, SMA and SMB, differing by a 7-residue peptide in loop 1 (i7) at the myosin active site where ATP is hydrolyzed. Using chicken isoforms, previous work indicated that the i7 deletion in SMA prolongs strong actin binding by inhibiting active site ingress and egress of nucleotide when compared to i7 inserted SMB. Additionally, i7 deletion inhibits Pi release associated with the switch 2 closed”śopen transition in actin-activated ATPase. Switch 2 is far from loop 1 indicating i7 deletion has an allosteric effect on Pi release. Chicken SMA and SMB have unknown and robust nucleotide-sensitive tryptophan (NST) fluorescence increments, respectively. Human SMA and SMB both lack NST increments while Pi release in Ca2+ATPase is not impacted by i7 deletion. The NST reports relay helix movement following conformation change in switch 2 but in the open”śclosed transition. The NST is common to all known myosin isoforms except human smooth muscle. Other independent works on human SMA and SMB motility indicate no functional effect of i7 deletion. Smooth muscle myosin is a stunning example of species-specific myosin structure/function divergence underscoring the danger in extrapolating disease-linked mutant effects on myosin across species. 1. Introduction Myosin is the chemomechanical energy transducer in muscle hydrolyzing ATP to power actin movement during contraction. It has a globular head domain called subfragment 1 (S1) and a tail domain that forms dimers. S1 contains an active site for ATP hydrolysis, an actin binding site, and a lever-arm whose rotary movement cyclically applies tension to cause contractility while myosin is strongly actin bound. Myosin energy transduction starts in the ATP binding site where peptides are linked to the 7-stranded -sheet sense position and coordination of the ATP -phosphate [1, 2]. ATP hydrolysis occurs rapidly, but products are not released until actin binds. The C-loop portion of the actin binding site senses actin contact that is transmitted to two strands in the 7-stranded -sheet, releasing product with the opening of switch 2 and translating the relay -helix [3]. Relay helix linear movement, sensed by the nucleotide sensitive tryptophan (NST) [4, 5], impinges on the converter changing linear force into torque to rotate the lever-arm. The lever-arm converts torque generated in the motor into the linear step-size displacement [6] and undergoes shear strain due to the resisting load [7]. Strain is shared among the lever-arm and the bound myosin light chains, essential (ELC)
%U http://www.hindawi.com/journals/isrn.structural.biology/2013/634341/