AN EXTENDED MICROTUBULE-BINDING STRUCTURE WITHIN THE DYNEIN MOTOR DOMAIN

Flagellar dynein was discovered over 30 years ago as the first motor p rotein capable of generating force along microtubules(1). A cytoplasmi c form of dynein has also been identified which is involved in mitosis and a wide range of other intracellular movement(2) (reviewed in ref. 3). Rapid progress has been made on understanding the mechanism of fo rce production by kinesins and myosins(4-8). In contrast, progress in understanding the dyneins has been limited by their great size (relati ve molecular mass 1,000K-2,000K) and subunit complexity. We now report evidence that the entire carboxy-terminal two-thirds of the 532K forc e-producing heavy chain subunit is required for ATP-binding activity. We further identify a microtubule-binding domain, which, surprisingly, lies well downstream of the entire ATPase region and is predicted to form a hairpin-like stalk Direct ultrastructural analysis of a recombi nant fragment confirms this model, and suggests that the mechanism for dynein force production differs substantially from that of other moto r proteins.