Kinesin

From Proteopedia

(Redirected from KIF)

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

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) residues 1-375, 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 are organized into 14 families named kinesin-1 to kinesin-14. 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.

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^[4].

Structural highlights

. Water molecules shown as red spheres. Residue . Arg216 pivots to enable release or the phosphate release. 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^[5].

3D Structures of Kinesin

Kinesin 3D Structures

References

↑ 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
↑ 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
↑ 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
↑ Grosch M, Gruner B, Spranger S, Stutz AM, Rausch T, Korbel JO, Seelow D, Nurnberg P, Sticht H, Lausch E, Zabel B, Winterpacht A, Tagariello A. Identification of a Ninein (NIN) mutation in a family with spondyloepimetaphyseal dysplasia with joint laxity (leptodactylic type)-like phenotype. Matrix Biol. 2013 Oct-Nov;32(7-8):387-92. doi: 10.1016/j.matbio.2013.05.001. Epub, 2013 May 9. PMID:23665482 doi:http://dx.doi.org/10.1016/j.matbio.2013.05.001
↑ 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