Revealingly odd couples.

Abstract

A large organism such as a human being is composed of a staggering number of small factories (cells), each one producing a complete set of the macromolecular assemblies required for life. Most of these assemblies are needed throughout the body, but rather than establish a few high-capacity factories and a wide distribution network, organisms choose to make almost everything locally and distribute it over only minuscule distances, rarely more than a few tens of microns. Evidently transport is more expensive than massively redundant manufacturing capability. Is that why cells evolved so many different kinds of motors (≈100 in a typical cell), so that each may be tuned for performance in a small number of highly specialized tasks (1)? Whatever the reason, biological motors are numerous and diverse. The few features that motors have in common therefore attract attention from biologists fascinated by these remarkable machines. One intriguing common feature (2) is that most biological motors are “two-headed” molecules (see Fig. 1), homodimeric proteins with two identical globular “heads” (“core motor domains” responsible for generating motion), held together by two entwined “tails” (long α-helices in a coiled-coil that terminates in a cargo attachment site). Although speculations abound, a convincing explanation for the functional significance of two-headedness is still missing. A major current thrust in the study of motility is to understand whether the two heads act independently or together, sequentially or simultaneously, undergoing the same or different structural transitions. In a recent issue of PNAS, a paper by Kaseda et al. (3) demonstrates a new, elegantly simple strategy for investigating these issues and provides some puzzling results that starkly reveal how little we know about even the most common biological motors. Fig 1. The core motor domains (“heads”) and part of the “necks” (the two vertically oriented α-helices) of dimeric rat kinesin, from …