Effects and dynamics of the UNC-45B molecular chaperone


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Each myosin molecule can generate ≈2pN of force, and each individual sarcomere can generate ≈32nN/μm2, but working together the muscles of the body can allow a human to deadlift up to 512kg. All of that force generation comes from the myosin motor domain, an 110kDa globular protein that allows conversion of the chemical potential energy in ATP into mechanical work. This complex protein is incapable of self-folding and assembly. Instead, the molecular chaperones work in a precise network to allow a nascent polypeptide to be protected from aggregation and folded to the precisely native product. The assembly of this myosin into a thick filament can proceed largely from the self-directed condensation of the myosin rods. However, this has never been sufficient to generate a thick filament in vivo. There is a complex interplay of myosin binding proteins making up the M-line, giant proteins spanning the sarcomere, and a lattice of thin filaments anchored by z-line proteins. There is now much evidence that in addition to allowing folding and preventing aggregation that molecular chaperones, including UNC-45B, play a role in thick filament assembly and organization. Further, in the act of performing extraordinary physical feats from a strongman’s deadlift through to a cheetahs sprint, muscle is stressed physically, chemically and thermally. Molecular chaperones likely play a key role in keeping this most dynamic of systems functioning despite a multitude of stressors.



Myosin, molecular chaperones, protein folding, muscle