5jv3

From Proteopedia

(Difference between revisions)

Current revision

The neck-linker and alpha 7 helix of Homo sapiens Eg5 fused to EB1

Structural highlights

5jv3 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.006Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KIF11_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]

Function

MARE1_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 PubMed

Kinesin-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

↑ Ostergaard P, Simpson MA, Mendola A, Vasudevan P, Connell FC, van Impel A, Moore AT, Loeys BL, Ghalamkarpour A, Onoufriadis A, Martinez-Corral I, Devery S, Leroy JG, van Laer L, Singer A, Bialer MG, McEntagart M, Quarrell O, Brice G, Trembath RC, Schulte-Merker S, Makinen T, Vikkula M, Mortimer PS, Mansour S, Jeffery S. Mutations in KIF11 cause autosomal-dominant microcephaly variably associated with congenital lymphedema and chorioretinopathy. Am J Hum Genet. 2012 Feb 10;90(2):356-62. doi: 10.1016/j.ajhg.2011.12.018. Epub, 2012 Jan 26. PMID:22284827 doi:10.1016/j.ajhg.2011.12.018
↑ Askham JM, Vaughan KT, Goodson HV, Morrison EE. Evidence that an interaction between EB1 and p150(Glued) is required for the formation and maintenance of a radial microtubule array anchored at the centrosome. Mol Biol Cell. 2002 Oct;13(10):3627-45. PMID:12388762 doi:10.1091/mbc.E02-01-0061
↑ van der Vaart B, Manatschal C, Grigoriev I, Olieric V, Gouveia SM, Bjelic S, Demmers J, Vorobjev I, Hoogenraad CC, Steinmetz MO, Akhmanova A. SLAIN2 links microtubule plus end-tracking proteins and controls microtubule growth in interphase. J Cell Biol. 2011 Jun 13;193(6):1083-99. Epub 2011 Jun 6. PMID:21646404 doi:10.1083/jcb.201012179
↑ Hayashi I, Wilde A, Mal TK, Ikura M. Structural basis for the activation of microtubule assembly by the EB1 and p150Glued complex. Mol Cell. 2005 Aug 19;19(4):449-60. PMID:16109370 doi:10.1016/j.molcel.2005.06.034
↑ Honnappa S, Gouveia SM, Weisbrich A, Damberger FF, Bhavesh NS, Jawhari H, Grigoriev I, van Rijssel FJ, Buey RM, Lawera A, Jelesarov I, Winkler FK, Wuthrich K, Akhmanova A, Steinmetz MO. An EB1-binding motif acts as a microtubule tip localization signal. Cell. 2009 Jul 23;138(2):366-76. PMID:19632184 doi:S0092-8674(09)00638-2
↑ Rapley J, Nicolas M, Groen A, Regue L, Bertran MT, Caelles C, Avruch J, Roig J. The NIMA-family kinase Nek6 phosphorylates the kinesin Eg5 at a novel site necessary for mitotic spindle formation. J Cell Sci. 2008 Dec 1;121(Pt 23):3912-21. doi: 10.1242/jcs.035360. Epub 2008 Nov, 11. PMID:19001501 doi:10.1242/jcs.035360
↑ Phillips RK, Peter LG, Gilbert SP, Rayment I. Family-specific kinesin structures reveal neck-linker length based on initiation of the coiled-coil. J Biol Chem. 2016 Jul 26. pii: jbc.M116.737577. PMID:27462072 doi:http://dx.doi.org/10.1074/jbc.M116.737577

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jv3"

Categories: Homo sapiens | Large Structures | Phillips RK | Rayment I

@@ Line 1: / Line 1: @@
 ==The neck-linker and alpha 7 helix of Homo sapiens Eg5 fused to EB1==
-<StructureSection load='5jv3' size='340' side='right' caption='[[5jv3]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
+<StructureSection load='5jv3' size='340' side='right'caption='[[5jv3]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jv3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JV3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JV3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jv3]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JV3 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.006&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jvm|5jvm]], [[5jvp|5jvp]], [[5jvr|5jvr]], [[5jvs|5jvs]], [[5jvu|5jvu]], [[5jx1|5jx1]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jv3 OCA], [http://pdbe.org/5jv3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jv3 RCSB], [http://www.ebi.ac.uk/pdbsum/5jv3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jv3 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5jv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jv3 OCA], [https://pdbe.org/5jv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jv3 RCSB], [https://www.ebi.ac.uk/pdbsum/5jv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jv3 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN]] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[http://omim.org/entry/152950 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.<ref>PMID:22284827</ref>
+[https://www.uniprot.org/uniprot/KIF11_HUMAN KIF11_HUMAN] Defects in KIF11 are the cause of microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) [MIM:[https://omim.org/entry/152950 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.<ref>PMID:22284827</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/KIF11_HUMAN 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.<ref>PMID:19001501</ref>
+[https://www.uniprot.org/uniprot/MARE1_HUMAN MARE1_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.<ref>PMID:12388762</ref> <ref>PMID:21646404</ref> <ref>PMID:16109370</ref> <ref>PMID:19632184</ref> [https://www.uniprot.org/uniprot/KIF11_HUMAN 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.<ref>PMID:19001501</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Phillips, R K]]
+[[Category: Homo sapiens]]
-[[Category: Rayment, I]]
+[[Category: Large Structures]]
-[[Category: Coiled-coil]]
+[[Category: Phillips RK]]
-[[Category: Kinesin]]
+[[Category: Rayment I]]
-[[Category: Motor protein]]

5jv3

From Proteopedia

Current revision

The neck-linker and alpha 7 helix of Homo sapiens Eg5 fused to EB1

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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