5mle

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of Human Dihydropyrimidinease-like 2 (DPYSL2A)/Collapsin Response Mediator Protein (CRMP2 13-516) Mutant Y479E/Y499E

Structural highlights

5mle is a 2 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 2.48Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

DPYL2_HUMAN Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (By similarity). Plays a role in neuron projection morphogenesis.^[1] ^[2]

Publication Abstract from PubMed

Though used widely in cancer therapy, paclitaxel only elicits a response in a fraction of patients. A strong determinant of paclitaxel tumor response is the state of microtubule dynamic instability. However, whether the manipulation of this physiological process can be controlled to enhance paclitaxel response has not been tested. Here, we show a previously unrecognized role of the microtubule-associated protein CRMP2 in inducing microtubule bundling through its carboxy terminus. This activity is significantly decreased when the FER tyrosine kinase phosphorylates CRMP2 at Y479 and Y499. The crystal structures of wild-type CRMP2 and CRMP2-Y479E reveal how mimicking phosphorylation prevents tetramerization of CRMP2. Depletion of FER or reducing its catalytic activity using sub-therapeutic doses of inhibitors increases paclitaxel-induced microtubule stability and cytotoxicity in ovarian cancer cells and in vivo. This work provides a rationale for inhibiting FER-mediated CRMP2 phosphorylation to enhance paclitaxel on-target activity for cancer therapy.

Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation.,Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, Masuda K, Karaminejadranjbar M, Mannion D, Miranda F, Herrero-Gonzalez S, Hellner K, Chen F, Alsaadi A, Albukhari A, Fotso DC, Yau C, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Knapp S, Gray NS, Campo L, Myers KA, Dhar S, Ferguson D, Bast RC Jr., Sood AK, von Delft F, Ahmed AA Nat Commun. 2018 Feb 2;9(1):476. doi: 10.1038/s41467-017-02811-7. PMID:29396402^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Inagaki N, Chihara K, Arimura N, Menager C, Kawano Y, Matsuo N, Nishimura T, Amano M, Kaibuchi K. CRMP-2 induces axons in cultured hippocampal neurons. Nat Neurosci. 2001 Aug;4(8):781-2. PMID:11477421 doi:http://dx.doi.org/10.1038/90476
↑ Cole AR, Knebel A, Morrice NA, Robertson LA, Irving AJ, Connolly CN, Sutherland C. GSK-3 phosphorylation of the Alzheimer epitope within collapsin response mediator proteins regulates axon elongation in primary neurons. J Biol Chem. 2004 Nov 26;279(48):50176-80. Epub 2004 Oct 5. PMID:15466863 doi:http://dx.doi.org/10.1074/jbc.C400412200
↑ Zheng Y, Sethi R, Mangala LS, Taylor C, Goldsmith J, Wang M, Masuda K, Karaminejadranjbar M, Mannion D, Miranda F, Herrero-Gonzalez S, Hellner K, Chen F, Alsaadi A, Albukhari A, Fotso DC, Yau C, Jiang D, Pradeep S, Rodriguez-Aguayo C, Lopez-Berestein G, Knapp S, Gray NS, Campo L, Myers KA, Dhar S, Ferguson D, Bast RC Jr., Sood AK, von Delft F, Ahmed AA. Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation. Nat Commun. 2018 Feb 2;9(1):476. doi: 10.1038/s41467-017-02811-7. PMID:29396402 doi:http://dx.doi.org/10.1038/s41467-017-02811-7

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='5mle' size='340' side='right'caption='[[5mle]], [[Resolution|resolution]] 2.48&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mle]] 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=5MLE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MLE FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mle]] is a 2 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=5MLE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MLE FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 2.48&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DPYSL2, CRMP2, ULIP2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=5mle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mle OCA], [http://pdbe.org/5mle PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mle RCSB], [http://www.ebi.ac.uk/pdbsum/5mle PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mle 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=5mle FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mle OCA], [https://pdbe.org/5mle PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mle RCSB], [https://www.ebi.ac.uk/pdbsum/5mle PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mle ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DPYL2_HUMAN DPYL2_HUMAN]] Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (By similarity). Plays a role in neuron projection morphogenesis.<ref>PMID:11477421</ref> <ref>PMID:15466863</ref>
+[https://www.uniprot.org/uniprot/DPYL2_HUMAN DPYL2_HUMAN] Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (By similarity). Plays a role in neuron projection morphogenesis.<ref>PMID:11477421</ref> <ref>PMID:15466863</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Ahmed, A A]]
+[[Category: Ahmed AA]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Delft, F von]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M]]
+[[Category: Sethi R]]
-[[Category: Sethi, R]]
+[[Category: Talon R]]
-[[Category: Talon, R]]
+[[Category: Velupillai S]]
-[[Category: Velupillai, S]]
+[[Category: Zheng Y]]
-[[Category: Zheng, Y]]
+[[Category: Von Delft F]]
-[[Category: Crmp2]]
-[[Category: Hydrolase]]
-[[Category: Microtubule associated protein]]
-[[Category: Ovarian cancer]]
-[[Category: Phospho-mutant]]

5mle

From Proteopedia

Current revision

Crystal Structure of Human Dihydropyrimidinease-like 2 (DPYSL2A)/Collapsin Response Mediator Protein (CRMP2 13-516) Mutant Y479E/Y499E

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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