α-Tropomyosin Knockouts

Structural analysis of smooth muscle tropomyosin α and β isoforms.

A large number of tropomyosin (Tm) isoforms function as gatekeepers of the actin filament, controlling the spatiotemporal access of actin-binding proteins to specialized actin networks. Residues ∼40-80 vary significantly among Tm isoforms, but the impact of sequence variation on Tm structure and interactions with actin is poorly understood, because structural studies have focused on skeletal mu...

α-Tropomyosin with a D175N or E180G Mutation in Only One Chain Differs from Tropomyosin with Mutations in Both Chains

α-Tropomyosin (Tm) carrying hypertrophic cardiomyopathy mutation D175N or E180G was expressed in Escherichia coli. We have assembled dimers of two polypeptide chains in vitro that carry one (αα*) or two (α*α*) copies of the mutation. We found that the presence of the mutation has little effect on dimer assembly, thereby predicting that individuals heterozygous for the Tm mutations are likely to...

The earliest knockouts.

Hormone-Sensitive Lipase Knockouts

All treatments for obesity, including dietary restriction of carbohydrates, have a goal of reducing the storage of fat in adipocytes. The chief enzyme responsible for the mobilization of FFA from adipose tissue, i.e., lipolysis, is thought to be hormone-sensitive lipase (HSL). Studies of HSL knockouts have provided important insights into the functional significance of HSL and into adipose meta...

Knockouts, Robustness and Cell Cycles

The response to a knockout of a node is a characteristic feature of a networked dynamical system. Knockout resilience in the dynamics of the remaining nodes is a sign of robustness. Here we study the effect of knockouts for binary state sequences and their implementations in terms of Boolean threshold networks. Beside random sequences with biologically plausible constraints, we analyze the cell...