This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
<table><tr><td colspan='2'>[[4uxs]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UXS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UXS FirstGlance]. <br>
<table><tr><td colspan='2'>[[4uxs]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UXS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UXS FirstGlance]. <br>
Line 28:
Line 28:
<references/>
<references/>
__TOC__
__TOC__
-
</StructureSection>
+
</SX>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
[[Category: Human]]
[[Category: Human]]
Revision as of 17:59, 6 March 2020
Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins
4uxs is a 3 chain structure with sequence from Bos taurus and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[KIF1A_HUMAN] Autosomal dominant nonsyndromic intellectual disability;Hereditary sensory and autonomic neuropathy type 2;Autosomal recessive spastic paraplegia type 30. The disease is caused by mutations affecting the gene represented in this entry.[1] The disease is caused by mutations affecting the gene represented in this entry.[2] The disease is caused by mutations affecting the gene represented in this entry.[3]
Function
[TBA1B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain. [KIF1A_HUMAN] Motor for anterograde axonal transport of synaptic vesicle precursors (By similarity). [TBB2B_BOVIN] Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha chain (By similarity).
Publication Abstract from PubMed
Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles - including their nucleotide-free states - at ~7A resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin-microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface.
Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins.,Atherton J, Farabella I, Yu IM, Rosenfeld SS, Houdusse A, Topf M, Moores CA Elife. 2014 Sep 10:e03680. doi: 10.7554/eLife.03680. PMID:25209998[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑ Erlich Y, Edvardson S, Hodges E, Zenvirt S, Thekkat P, Shaag A, Dor T, Hannon GJ, Elpeleg O. Exome sequencing and disease-network analysis of a single family implicate a mutation in KIF1A in hereditary spastic paraparesis. Genome Res. 2011 May;21(5):658-64. doi: 10.1101/gr.117143.110. Epub 2011 Apr 12. PMID:21487076 doi:http://dx.doi.org/10.1101/gr.117143.110
↑ Riviere JB, Ramalingam S, Lavastre V, Shekarabi M, Holbert S, Lafontaine J, Srour M, Merner N, Rochefort D, Hince P, Gaudet R, Mes-Masson AM, Baets J, Houlden H, Brais B, Nicholson GA, Van Esch H, Nafissi S, De Jonghe P, Reilly MM, Timmerman V, Dion PA, Rouleau GA. KIF1A, an axonal transporter of synaptic vesicles, is mutated in hereditary sensory and autonomic neuropathy type 2. Am J Hum Genet. 2011 Aug 12;89(2):219-30. doi: 10.1016/j.ajhg.2011.06.013. Epub, 2011 Aug 4. PMID:21820098 doi:http://dx.doi.org/10.1016/j.ajhg.2011.06.013
↑ Hamdan FF, Gauthier J, Araki Y, Lin DT, Yoshizawa Y, Higashi K, Park AR, Spiegelman D, Dobrzeniecka S, Piton A, Tomitori H, Daoud H, Massicotte C, Henrion E, Diallo O, Shekarabi M, Marineau C, Shevell M, Maranda B, Mitchell G, Nadeau A, D'Anjou G, Vanasse M, Srour M, Lafreniere RG, Drapeau P, Lacaille JC, Kim E, Lee JR, Igarashi K, Huganir RL, Rouleau GA, Michaud JL. Excess of de novo deleterious mutations in genes associated with glutamatergic systems in nonsyndromic intellectual disability. Am J Hum Genet. 2011 Mar 11;88(3):306-16. doi: 10.1016/j.ajhg.2011.02.001. Epub, 2011 Mar 3. PMID:21376300 doi:10.1016/j.ajhg.2011.02.001
↑ Atherton J, Farabella I, Yu IM, Rosenfeld SS, Houdusse A, Topf M, Moores CA. Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins. Elife. 2014 Sep 10:e03680. doi: 10.7554/eLife.03680. PMID:25209998 doi:http://dx.doi.org/10.7554/eLife.03680
