Dataset Information

A cool look at the structural changes in kinesin motor domains.

ABSTRACT: Recently, several 3D images of kinesin-family motor domains interacting with microtubules have been obtained by analysis of electron microscope images of frozen hydrated complexes at much higher resolutions (9-12 A) than in previous reports (15-30 A). The high-resolution maps show a complex interaction interface between kinesin and tubulin, in which kinesin's switch II helix alpha4 is a central feature. Differences due to the presence of ADP, as compared with ATP analogues, support previously determined crystal structures of kinesins alone in suggesting that alpha4 is part of a pathway linking the nucleotide-binding site and the neck that connects to cargo. A 3D structure of the microtubule-bound Kar3 motor domain in a nucleotide-free state has revealed dramatic changes not yet reported for any crystal structure, including melting of the switch II helix, that may be part of the mechanism by which information is transmitted. A nucleotide-dependent movement of helix alpha6, first seen in crystal structures of Kif1a, appears to bring it into contact with tubulin and may provide another communication link. A microtubule-induced movement of loop L7 and a related distortion of the central beta-sheet, detected only in the empty state, may also send a signal to the region of the motor core that interacts with the neck. Earlier images of a kinesin-1 dimer in the empty state, showing a close interaction between the two motor heads, can now be interpreted in terms of a communication route from the active site of the directly bound head via its central beta-sheet to the tethered head.

SUBMITTER: Amos LA

PROVIDER: S-EPMC2505108 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A cool look at the structural changes in kinesin motor domains.

Amos Linda A LA Hirose Keiko K

Journal of cell science 20071101 Pt 22

Recently, several 3D images of kinesin-family motor domains interacting with microtubules have been obtained by analysis of electron microscope images of frozen hydrated complexes at much higher resolutions (9-12 A) than in previous reports (15-30 A). The high-resolution maps show a complex interaction interface between kinesin and tubulin, in which kinesin's switch II helix alpha4 is a central feature. Differences due to the presence of ADP, as compared with ATP analogues, support previously de ...[more]

PMID: 17989090

Similar Datasets

Project description:Kinesin motor proteins drive intracellular transport by coupling ATP hydrolysis to conformational changes that mediate directed movement along microtubules. Characterizing these distinct conformations and their interconversion mechanism is essential to determining an atomic-level model of kinesin action. Here we report a comprehensive principal component analysis of 114 experimental structures along with the results of conventional and accelerated molecular dynamics simulations that together map the structural dynamics of the kinesin motor domain. All experimental structures were found to reside in one of three distinct conformational clusters (ATP-like, ADP-like and Eg5 inhibitor-bound). These groups differ in the orientation of key functional elements, most notably the microtubule binding α4-α5, loop8 subdomain and α2b-β4-β6-β7 motor domain tip. Group membership was found not to correlate with the nature of the bound nucleotide in a given structure. However, groupings were coincident with distinct neck-linker orientations. Accelerated molecular dynamics simulations of ATP, ADP and nucleotide free Eg5 indicate that all three nucleotide states could sample the major crystallographically observed conformations. Differences in the dynamic coupling of distal sites were also evident. In multiple ATP bound simulations, the neck-linker, loop8 and the α4-α5 subdomain display correlated motions that are absent in ADP bound simulations. Further dissection of these couplings provides evidence for a network of dynamic communication between the active site, microtubule-binding interface and neck-linker via loop7 and loop13. Additional simulations indicate that the mutations G325A and G326A in loop13 reduce the flexibility of these regions and disrupt their couplings. Our combined results indicate that the reported ATP and ADP-like conformations of kinesin are intrinsically accessible regardless of nucleotide state and support a model where neck-linker docking leads to a tighter coupling of the microtubule and nucleotide binding regions. Furthermore, simulations highlight sites critical for large-scale conformational changes and the allosteric coupling between distal functional sites.

Dataset Information

A cool look at the structural changes in kinesin motor domains.

Publications

A cool look at the structural changes in kinesin motor domains.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets