Structural Biology

Biography

Biography: Kenneth A Taylor

Abstract

Many biological systems contain complex mixtures of filaments, such as actin containing and myosin containing filaments and the cytoskeleton. The properties of the interacting partners are keys to understanding how the systems function. In muscle, the filament systems are composed of multiple proteins that modify the basic filament. In the case of actin, the troponin-tropomyosin system provides a mechanism for regulating attachment by the myosin motors and thus muscle contraction. During muscle contraction, myosin motors attach the thin filament in multiple ways producing a heterogeneous system that is difficult to dissect. Many proteins interact with F-actin to form cross-linked bundles. Among these are fimbrin, villin, α-actinin and several glycolytic enzymes and even elevated concentrations of magnesium and polylysine. An im­portant characteristic of these cross-linkers is an ability to form 2-D rafts on positively charged lipid monolayers. Actin rafts should be ideal for structure determination by electron micros­copy (EM) but several problems exist, in particular heterogeneity. All raft cross-linkers produce polymorphic rafts that are either polar or have mixed polarity. Even bundles of defined polarity can have heterogeneous cross linkers. We have developed a strategy for obtaining information from these heterogeneous systems using sub-volume alignment and classification that will be applicable to this type of problem and perhaps many others where there is difficulty obtaining large populations of homogeneous entities, be they filament segments or single particles.