5jv3 | pdb_00005jv3
The neck-linker and alpha 7 helix of Homo sapiens Eg5 fused to EB1
Structural highlights
DiseaseKIF11_HUMAN Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:152950. An autosomal dominant disorder that involves an overlapping but variable spectrum of central nervous system and ocular developmental anomalies. Microcephaly ranges from mild to severe and is often associated with mild to moderate developmental delay and a characteristic facial phenotype with upslanting palpebral fissures, broad nose with rounded tip, long philtrum with thin upper lip, prominent chin, and prominent ears. Chorioretinopathy is the most common eye abnormality, but retinal folds, microphthalmia, and myopic and hypermetropic astigmatism have also been reported, and some individuals have no overt ocular phenotype. Congenital lymphedema, when present, is typically confined to the dorsa of the feet, and lymphoscintigraphy reveals the absence of radioactive isotope uptake from the webspaces between the toes.[1] 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.[2] [3] [4] [5] KIF11_HUMAN Motor protein required for establishing a bipolar spindle. Blocking of KIF11 prevents centrosome migration and arrest cells in mitosis with monoastral microtubule arrays.[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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