Kinesin

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Template:STRUCTURE 2zfi

Contents 1 Function 2 Disease 3 Structural highlights 4 3D Structures of Kinesin 5 References

Function

Kinesins are eukaryotic motor proteins which move along microtubules^[1]. Kinesin (KIF) is a dimer consisting of 2 heavy chains and two light chains. The heavy chain contains the N-terminal globular motor domain (MD) responsible for the motor activity of kinesin, a central flexible neck linker (FNL) coiled-coil stalk which intertwines to form the dimer and a small globular C-terminal domain which interacts with other proteins like the kinesin light chain. The light chain (KLC) forms the tail region. The KLC contains a cargo binding domain which is called TPR (Tetratricopeptide repeat). The KIFs are named by their gene number. KIF contains a forkhead-associated domain (FHA) which is involved in phosphopeptide recognition.

• KIF1A transports organelles along axonal microtubules.
  
• KIF1C and KIF2 are plus-ended directed microtubule motors.
  
• KIF2C, KIF22 and KIF3B are plus-ended directed microtubule motors in mitotic cells
  
• KIF13B transports VEGFR2 from the Golgi to the endothelial cell surface.
  
• KIF16B is plus-ended directed microtubule motor involved in endosome transport and receptor recycling.
  
• KIFC1 transports DNA molecules along cytoskeleton filaments.
  
• Kar3 is kinesin protein in yeast.
  
• Eg5 or KIF11 is a kinesin (See Kinesin-5) which participates in mitosis.
  
• NOD is a Drosophila chromosome-associated kinesin.

See also CAP-Gly domain.

Disease

Mutations in KIF5A are involved in hereditary spastic paraplegia^[2]. Mutation in KIF1B is the cause of Charcot-Marie-Tooth disease ^[3]. Mutations in KIF22 cause spondyloepimetaphyseal dysplasia.

Structural highlights

Residue Arg216 is the key residue in KIF for the chemical cycling of ATPase and for the mechanical cycling. Arg216 pivots to enable Mg-ADP release or the phosphate release. Arg216 forms a latch in the KIF 'closed-state' before the Mg-ADP release. Binding of β-tubulin to KIF releases the latch, enabling the KIF conformation change and detaching KIF from the microtubule and enabling the next movement cycle^[4].

3D Structures of Kinesin

Updated on 07-April-2016

References

1. ↑ Hirokawa N, Noda Y, Tanaka Y, Niwa S. Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol. 2009 Oct;10(10):682-96. doi: 10.1038/nrm2774. PMID:19773780 doi:http://dx.doi.org/10.1038/nrm2774
2. ↑ Ebbing B, Mann K, Starosta A, Jaud J, Schols L, Schule R, Woehlke G. Effect of spastic paraplegia mutations in KIF5A kinesin on transport activity. Hum Mol Genet. 2008 May 1;17(9):1245-52. doi: 10.1093/hmg/ddn014. Epub 2008 Jan, 18. PMID:18203753 doi:http://dx.doi.org/10.1093/hmg/ddn014
3. ↑ Hirokawa N, Takemura R. Biochemical and molecular characterization of diseases linked to motor proteins. Trends Biochem Sci. 2003 Oct;28(10):558-65. PMID:14559185 doi:http://dx.doi.org/10.1016/j.tibs.2003.08.006
4. ↑ Nitta R, Okada Y, Hirokawa N. Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin. Nat Struct Mol Biol. 2008 Oct;15(10):1067-75. Epub 2008 Sep 21. PMID:18806800 doi:10.1038/nsmb.1487