| Structural highlights
Function
[TBA1B_PIG] 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. [PRC1_HUMAN] Key regulator of cytokinesis that cross-links antiparrallel microtubules at an average distance of 35 nM. Essential for controlling the spatiotemporal formation of the midzone and successful cytokinesis. Required for KIF14 localization to the central spindle and midbody. Required to recruit PLK1 to the spindle. Stimulates PLK1 phosphorylation of RACGAP1 to allow recruitment of ECT2 to the central spindle.[1] [2] [3] [4] [5] [6] [7] [TBB_PIG] 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.
Publication Abstract from PubMed
Proteins that associate with microtubules (MTs) are crucial to generate MT arrays and establish different cellular architectures. One example is PRC1 (protein regulator of cytokinesis 1), which cross-links antiparallel MTs and is essential for the completion of mitosis and cytokinesis. Here we describe a 4-A-resolution cryo-EM structure of monomeric PRC1 bound to MTs. Residues in the spectrin domain of PRC1 contacting the MT are highly conserved and interact with the same pocket recognized by kinesin. We additionally found that PRC1 promotes MT assembly even in the presence of the MT stabilizer taxol. Interestingly, the angle of the spectrin domain on the MT surface corresponds to the previously observed cross-bridge angle between MTs cross-linked by full-length, dimeric PRC1. This finding, together with molecular dynamic simulations describing the intrinsic flexibility of PRC1, suggests that the MT-spectrin domain interface determines the geometry of the MT arrays cross-linked by PRC1.
Near-atomic cryo-EM structure of PRC1 bound to the microtubule.,Kellogg EH, Howes S, Ti SC, Ramirez-Aportela E, Kapoor TM, Chacon P, Nogales E Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9430-9. doi:, 10.1073/pnas.1609903113. Epub 2016 Aug 4. PMID:27493215[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jiang W, Jimenez G, Wells NJ, Hope TJ, Wahl GM, Hunter T, Fukunaga R. PRC1: a human mitotic spindle-associated CDK substrate protein required for cytokinesis. Mol Cell. 1998 Dec;2(6):877-85. PMID:9885575
- ↑ Mollinari C, Kleman JP, Jiang W, Schoehn G, Hunter T, Margolis RL. PRC1 is a microtubule binding and bundling protein essential to maintain the mitotic spindle midzone. J Cell Biol. 2002 Jun 24;157(7):1175-86. Epub 2002 Jun 24. PMID:12082078 doi:10.1083/jcb.200111052
- ↑ Kurasawa Y, Earnshaw WC, Mochizuki Y, Dohmae N, Todokoro K. Essential roles of KIF4 and its binding partner PRC1 in organized central spindle midzone formation. EMBO J. 2004 Aug 18;23(16):3237-48. Epub 2004 Aug 5. PMID:15297875 doi:10.1038/sj.emboj.7600347
- ↑ Zhu C, Jiang W. Cell cycle-dependent translocation of PRC1 on the spindle by Kif4 is essential for midzone formation and cytokinesis. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):343-8. Epub 2004 Dec 29. PMID:15625105 doi:0408438102
- ↑ Gruneberg U, Neef R, Li X, Chan EH, Chalamalasetty RB, Nigg EA, Barr FA. KIF14 and citron kinase act together to promote efficient cytokinesis. J Cell Biol. 2006 Jan 30;172(3):363-72. Epub 2006 Jan 23. PMID:16431929 doi:jcb.200511061
- ↑ Wolfe BA, Takaki T, Petronczki M, Glotzer M. Polo-like kinase 1 directs assembly of the HsCyk-4 RhoGAP/Ect2 RhoGEF complex to initiate cleavage furrow formation. PLoS Biol. 2009 May 5;7(5):e1000110. doi: 10.1371/journal.pbio.1000110. Epub 2009, May 26. PMID:19468300 doi:10.1371/journal.pbio.1000110
- ↑ Subramanian R, Wilson-Kubalek EM, Arthur CP, Bick MJ, Campbell EA, Darst SA, Milligan RA, Kapoor TM. Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein. Cell. 2010 Aug 6;142(3):433-43. PMID:20691902 doi:10.1016/j.cell.2010.07.012
- ↑ Kellogg EH, Howes S, Ti SC, Ramirez-Aportela E, Kapoor TM, Chacon P, Nogales E. Near-atomic cryo-EM structure of PRC1 bound to the microtubule. Proc Natl Acad Sci U S A. 2016 Aug 23;113(34):9430-9. doi:, 10.1073/pnas.1609903113. Epub 2016 Aug 4. PMID:27493215 doi:http://dx.doi.org/10.1073/pnas.1609903113
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