5jvp
The neck-linker and alpha 7 helix of Homo sapiens CENP-E
Structural highlights
FunctionMARE1_HUMAN Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. May be involved in spindle function by stabilizing microtubules and anchoring them at centrosomes. May play a role in cell migration.[1] [2] [3] [4] CENPE_HUMAN Essential for the maintenance of chromosomal stability through efficient stabilization of microtubule capture at kinetochores. Plays a key role in the movement of chromosomes toward the metaphase plate during mitosis. Is a slow plus end-directed motor whose activity is essential for metaphase chromosome alignment. Couples chromosome position to microtubule depolymerizing activity. The highly processive microtubule-dependent motor activity of CENPE serves to power chromosome congression and provides a flexible, motile tether linking kinetochores to dynamic spindle microtubules. Necessary for the mitotic checkpoint signal at individual kinetochores to prevent aneuploidy due to single chromosome loss. Required for the efficient recruitment of BUBR1, MAD1 and MAD2 to attached and newly unattached kinetochores. Stimulates mammalian BUBR1 kinase activity. Accumulates just before mitosis at the G2 phase of the cell cycle.[5] [6] Publication Abstract from PubMedKinesin-1, 2, 5, and 7 generate processive hand-over-hand 8-nm steps to transport intracellular cargoes toward the microtubule plus end. This processive motility requires gating mechanisms to coordinate the mechanochemical cycles of the two motor heads to sustain the processive run. A key structural element believed to regulate the degree of processivity is the neck-linker, a short peptide of 12-18 residues, which connects the motor domain to its coiled-coil stalk. While a shorter neck-linker has been correlated with longer run lengths, the structural data to support this hypothesis have been lacking. To test this hypothesis, seven kinesin structures were determined by X-ray crystallography. Each included the neck-linker motif, followed by helix alpha7 which constitutes the start of the coiled-coil stalk. In the majority of the structures, the neck-linker length differed from predictions because helix alpha7, which initiates the coiled-coil, started earlier in the sequence than predicted. A further examination of structures in the PDB reveals that there is a great disparity between the predicted and observed starting residues. This suggests that an accurate prediction of the start of a coiled-coil is currently difficult to achieve. These results are significant because they now exclude simple comparisons between members of the kinesin superfamily and add a further layer of complexity when interpreting the results of mutagenesis or protein fusion. They also re-emphasize the need to consider factors beyond the kinesin neck-linker motif when attempting to understand how inter-head communication is tuned to achieve the degree of processivity required for cellular function. Family-specific kinesin structures reveal neck-linker length based on initiation of the coiled-coil.,Phillips RK, Peter LG, Gilbert SP, Rayment I J Biol Chem. 2016 Jul 26. pii: jbc.M116.737577. PMID:27462072[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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