1txq: Difference between revisions
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==Crystal structure of the EB1 C-terminal domain complexed with the CAP-Gly domain of p150Glued== | ==Crystal structure of the EB1 C-terminal domain complexed with the CAP-Gly domain of p150Glued== | ||
<StructureSection load='1txq' size='340' side='right' caption='[[1txq]], [[Resolution|resolution]] 1.80Å' scene=''> | <StructureSection load='1txq' size='340' side='right'caption='[[1txq]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[1txq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXQ OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[1txq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TXQ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1TXQ FirstGlance]. <br> | ||
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">p150Glued ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">p150Glued ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), EB1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1txq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1txq OCA], [http://pdbe.org/1txq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1txq RCSB], [http://www.ebi.ac.uk/pdbsum/1txq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1txq ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
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*[[Dynactin|Dynactin]] | *[[Dynactin|Dynactin]] | ||
*[[End-binding protein|End-binding protein]] | *[[End-binding protein|End-binding protein]] | ||
*[[Microtubule-associated protein|Microtubule-associated protein]] | *[[Microtubule-associated protein 3D structures|Microtubule-associated protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Hayashi, I]] | [[Category: Hayashi, I]] | ||
[[Category: Ikura, M]] | [[Category: Ikura, M]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Structural protein-protein binding complex]] | [[Category: Structural protein-protein binding complex]] | ||
Revision as of 15:03, 24 December 2020
Crystal structure of the EB1 C-terminal domain complexed with the CAP-Gly domain of p150GluedCrystal structure of the EB1 C-terminal domain complexed with the CAP-Gly domain of p150Glued
Structural highlights
Disease[DCTN1_HUMAN] Defects in DCTN1 are the cause of distal hereditary motor neuronopathy type 7B (HMN7B) [MIM:607641]; also known as progressive lower motor neuron disease (PLMND). HMN7B is a neuromuscular disorder. Distal hereditary motor neuronopathies constitute a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs.[1] [2] [3] [4] Defects in DCTN1 are a cause of susceptibility to amyotrophic lateral sclerosis (ALS) [MIM:105400]. ALS is a neurodegenerative disorder affecting upper and lower motor neurons, and resulting in fatal paralysis. Sensory abnormalities are absent. Death usually occurs within 2 to 5 years. The etiology is likely to be multifactorial, involving both genetic and environmental factors.[5] [6] Defects in DCTN1 are the cause of Perry syndrome (PERRYS) [MIM:168605]; also called parkinsonism with alveolar hypoventilation and mental depression. Perry syndrome is a neuropsychiatric disorder characterized by mental depression not responsive to antidepressant drugs or electroconvulsive therapy, sleep disturbances, exhaustion and marked weight loss. Parkinsonism develops later and respiratory failure occurred terminally.[7] Function[DCTN1_HUMAN] Required for the cytoplasmic dynein-driven retrograde movement of vesicles and organelles along microtubules. Dynein-dynactin interaction is a key component of the mechanism of axonal transport of vesicles and organelles. [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.[8] [9] [10] [11] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPlus-end tracking proteins, such as EB1 and the dynein/dynactin complex, regulate microtubule dynamics. These proteins are thought to stabilize microtubules by forming a plus-end complex at microtubule growing ends with ill-defined mechanisms. Here we report the crystal structure of two plus-end complex components, the carboxy-terminal dimerization domain of EB1 and the microtubule binding (CAP-Gly) domain of the dynactin subunit p150Glued. Each molecule of the EB1 dimer contains two helices forming a conserved four-helix bundle, while also providing p150Glued binding sites in its flexible tail region. Combining crystallography, NMR, and mutational analyses, our studies reveal the critical interacting elements of both EB1 and p150Glued, whose mutation alters microtubule polymerization activity. Moreover, removal of the key flexible tail from EB1 activates microtubule assembly by EB1 alone, suggesting that the flexible tail negatively regulates EB1 activity. We, therefore, propose that EB1 possesses an auto-inhibited conformation, which is relieved by p150Glued as an allosteric activator. Structural basis for the activation of microtubule assembly by the EB1 and p150Glued complex.,Hayashi I, Wilde A, Mal TK, Ikura M Mol Cell. 2005 Aug 19;19(4):449-60. PMID:16109370[12] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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