Autoinhibitory and other autoregulatory elements within the dynein motor domain

Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

“…Given the physical closeness between the nudAL1098F mutation and the deduced LIS1-binding site in the stem, one can speculate that NUDF/LIS1 binding causes a subtle conformational change of the stem region and that the L1098F mutation may partially mimic such a change. On the basis of deletion analyses and the analysis of trypsin digestion sites, the LIS1-binding site does not seem to be part of the linker domain that connects directly to the motor head domain (Gee et al 1997;Tai et al 2002;Hook et al 2005;Vallee and Hook 2006). Similarly, the A. nidulans nudAL1098F mutation, which corresponds to the L1060 residue in human dynein heavy chain, should also reside in the first part of the stem region rather than in the linker domain.…”

“…On the other hand, we do know that the nudAR3086C mutation that lowers dynein's ATPase activity by itself is recessive to the wild-type allele, which makes it harder to study its effect in a diploid system. However, the success in analyzing the ATPase cycle of recombinant dynein in vitro makes it possible to study these recessive mutations in higher systems (Hook et al 2005;Vallee and Hook 2006), and such studies are likely to generate new insights into the structural-functional relationship of the dynein heavy chain domains.…”

“…C YTOPLASMIC dynein is a microtubule motor that plays multiple roles in mitosis and organelle distribution and in transport of vesicles, proteins/mRNAs, and viruses (reviewed by Vale 2003;Greber and Way 2006;Levy and Holzbaur 2006;Vallee and Hook 2006). However, it is not yet clear how cytoplasmic dynein is targeted to various cellular locations and how its motor activity is regulated.…”

“…Electron microscopic analyses of a flagella dynein have suggested that the stem connects to the motor head through a linker 10 nm long, and a change in the orientation of the linker correlates with dynein power stroke that results in an 15-nm displacement of the tip of the microtubule-binding stalk (Burgess et al 2003). This linker may correspond to a region, 600 amino acids before the first AAA domain, which may affect the ATPase cycle of the AAA1 domain (Gee et al 1997;Vallee and Hook 2006). Taken together, the dynein motor is organized in a unique fashion different from other motors such as kinesins and myosins (King 2000;Asai and Koonce 2001;Burgess and Knight 2004;Koonce and Samso 2004;Vallee and Hook 2006).…”

“…This linker may correspond to a region, 600 amino acids before the first AAA domain, which may affect the ATPase cycle of the AAA1 domain (Gee et al 1997;Vallee and Hook 2006). Taken together, the dynein motor is organized in a unique fashion different from other motors such as kinesins and myosins (King 2000;Asai and Koonce 2001;Burgess and Knight 2004;Koonce and Samso 2004;Vallee and Hook 2006). The structure of the dynein motor is complex and also recent studies on dynein behaviors have added another layer of complexity onto this motor (Mallik et al 2004;Reck-Peterson et al 2006;Ross et al 2006;Toba et al 2006).…”