Functional Asymmetry in Kinesin and Dynein Dimers

Overview

Journal Biol Cell

Specialty Cell Biology

Date 2012 Oct 17

PMID 23066835

Citations 7

Authors

Katherine C Rank

Ivan Rayment

Affiliations

Soon will be listed here.

Abstract

Active transport along the microtubule lattice is a complex process that involves both the Kinesin and Dynein superfamily of motors. Transportation requires sophisticated regulation much of which occurs through the motor's tail domain. However, a significant portion of this regulation also occurs through structural changes that arise in the motor and the microtubule upon binding. The most obvious structural change being the manifestation of asymmetry. To a first approximation in solution, kinesin dimers exhibit twofold symmetry, and microtubules exhibit helical symmetry. The higher symmetries of both the kinesin dimers and microtubule lattice are lost on formation of the kinesin-microtubule complex. Loss of symmetry has functional consequences such as an asymmetric hand-over-hand mechanism in plus-end-directed kinesins, asymmetric microtubule binding in the Kinesin-14 family, spatially biased stepping in dynein and cooperative binding of additional motors to the microtubule. This review focusses on how the consequences of asymmetry affect regulation of motor heads within a dimer, dimers within an ensemble of motors, and suggests how these asymmetries may affect regulation of active transport within the cell.

Citing Articles

The ability of the kinesin-2 heterodimer KIF3AC to navigate microtubule networks is provided by the KIF3A motor domain.

Deeb S, Guzik-Lendrum S, Jeffrey J, Gilbert S J Biol Chem. 2019; 294(52):20070-20083.

PMID: 31748411 PMC: 6937563. DOI: 10.1074/jbc.RA119.010725.

Structural consequences of hereditary spastic paraplegia disease-related mutations in kinesin.

Dutta M, Diehl M, Onuchic J, Jana B Proc Natl Acad Sci U S A. 2018; 115(46):E10822-E10829.

PMID: 30366951 PMC: 6243270. DOI: 10.1073/pnas.1810622115.

Kinesin-2 motors: Kinetics and biophysics.

Gilbert S, Guzik-Lendrum S, Rayment I J Biol Chem. 2018; 293(12):4510-4518.

PMID: 29444824 PMC: 5868254. DOI: 10.1074/jbc.R117.001324.

Fast or Slow, Either Head Can Start the Processive Run of Kinesin-2 KIF3AC.

Zhang P, Rayment I, Gilbert S J Biol Chem. 2015; 291(9):4407-16.

PMID: 26710851 PMC: 4813469. DOI: 10.1074/jbc.M115.705970.

Kinesin-2 KIF3AC and KIF3AB Can Drive Long-Range Transport along Microtubules.

Guzik-Lendrum S, Rank K, Bensel B, Taylor K, Rayment I, Gilbert S Biophys J. 2015; 109(7):1472-82.

PMID: 26445448 PMC: 4601047. DOI: 10.1016/j.bpj.2015.08.004.

References

Mackey A, Gilbert S . Moving a microtubule may require two heads: a kinetic investigation of monomeric Ncd. Biochemistry. 2000; 39(6):1346-55. DOI: 10.1021/bi991918+. View

Fink G, Hajdo L, Skowronek K, Reuther C, Kasprzak A, Diez S . The mitotic kinesin-14 Ncd drives directional microtubule-microtubule sliding. Nat Cell Biol. 2009; 11(6):717-23. DOI: 10.1038/ncb1877. View

King S, Schroer T . Dynactin increases the processivity of the cytoplasmic dynein motor. Nat Cell Biol. 2000; 2(1):20-4. DOI: 10.1038/71338. View

Clamp M, Cuff J, Searle S, Barton G . The Jalview Java alignment editor. Bioinformatics. 2004; 20(3):426-7. DOI: 10.1093/bioinformatics/btg430. View

Jamison D, Driver J, Rogers A, Constantinou P, Diehl M . Two kinesins transport cargo primarily via the action of one motor: implications for intracellular transport. Biophys J. 2010; 99(9):2967-77. PMC: 2966006. DOI: 10.1016/j.bpj.2010.08.025. View

deCastro M, Ho C, Stewart R . Motility of dimeric ncd on a metal-chelating surfactant: evidence that ncd is not processive. Biochemistry. 1999; 38(16):5076-81. DOI: 10.1021/bi9829175. View

Waitzman J, Larson A, Cochran J, Naber N, Cooke R, Kull F . The loop 5 element structurally and kinetically coordinates dimers of the human kinesin-5, Eg5. Biophys J. 2012; 101(11):2760-9. PMC: 3297777. DOI: 10.1016/j.bpj.2011.10.032. View

Clancy B, Behnke-Parks W, Andreasson J, Rosenfeld S, Block S . A universal pathway for kinesin stepping. Nat Struct Mol Biol. 2011; 18(9):1020-7. PMC: 3167932. DOI: 10.1038/nsmb.2104. View

Svoboda K, Schmidt C, Schnapp B, Block S . Direct observation of kinesin stepping by optical trapping interferometry. Nature. 1993; 365(6448):721-7. DOI: 10.1038/365721a0. View

10.

Muto E, Sakai H, Kaseda K . Long-range cooperative binding of kinesin to a microtubule in the presence of ATP. J Cell Biol. 2005; 168(5):691-6. PMC: 2171822. DOI: 10.1083/jcb.200409035. View

11.

Shubeita G, Tran S, Xu J, Vershinin M, Cermelli S, Cotton S . Consequences of motor copy number on the intracellular transport of kinesin-1-driven lipid droplets. Cell. 2008; 135(6):1098-107. PMC: 2768369. DOI: 10.1016/j.cell.2008.10.021. View

12.

Asbury C, Fehr A, Block S . Kinesin moves by an asymmetric hand-over-hand mechanism. Science. 2003; 302(5653):2130-4. PMC: 1523256. DOI: 10.1126/science.1092985. View

13.

Hua W, Chung J, Gelles J . Distinguishing inchworm and hand-over-hand processive kinesin movement by neck rotation measurements. Science. 2002; 295(5556):844-8. DOI: 10.1126/science.1063089. View

14.

MURESAN V, Abramson T, Lyass A, Winter D, Porro E, Hong F . KIF3C and KIF3A form a novel neuronal heteromeric kinesin that associates with membrane vesicles. Mol Biol Cell. 1998; 9(3):637-52. PMC: 25292. DOI: 10.1091/mbc.9.3.637. View

15.

Kaseda K, Higuchi H, Hirose K . Alternate fast and slow stepping of a heterodimeric kinesin molecule. Nat Cell Biol. 2003; 5(12):1079-82. DOI: 10.1038/ncb1067. View

16.

Kaan H, Hackney D, Kozielski F . The structure of the kinesin-1 motor-tail complex reveals the mechanism of autoinhibition. Science. 2011; 333(6044):883-5. PMC: 3339660. DOI: 10.1126/science.1204824. View

17.

Hancock W, Howard J . Kinesin's processivity results from mechanical and chemical coordination between the ATP hydrolysis cycles of the two motor domains. Proc Natl Acad Sci U S A. 1999; 96(23):13147-52. PMC: 23915. DOI: 10.1073/pnas.96.23.13147. View

18.

Kon T, Oyama T, Shimo-Kon R, Imamula K, Shima T, Sutoh K . The 2.8 Å crystal structure of the dynein motor domain. Nature. 2012; 484(7394):345-50. DOI: 10.1038/nature10955. View

19.

Page B, Satterwhite L, Rose M, Snyder M . Localization of the Kar3 kinesin heavy chain-related protein requires the Cik1 interacting protein. J Cell Biol. 1994; 124(4):507-19. PMC: 2119913. DOI: 10.1083/jcb.124.4.507. View

20.

McIntosh J, Morphew M, Grissom P, Gilbert S, Hoenger A . Lattice structure of cytoplasmic microtubules in a cultured Mammalian cell. J Mol Biol. 2009; 394(2):177-82. PMC: 2784118. DOI: 10.1016/j.jmb.2009.09.033. View