3hbw: Difference between revisions

Latest revision as of 07:19, 6 September 2023

Crystal Structure of Human Fibroblast Growth Factor Homologous Factor 2A (FHF2A), also referred to as Fibroblast Growth Factor 13A (FGF13A)

Structural highlights

3hbw 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 1.9Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FGF13_HUMAN Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, may participate to the refinement of axons by negatively regulating axonal and leading processes branching. Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus.^[1] May regulate voltage-gated sodium channels transport and function.^[2] May also play a role in MAPK signaling.^[3]

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 PubMed

Voltage-gated sodium channels (Nav) produce sodium currents that underlie the initiation and propagation of action potentials in nerve and muscle cells. Fibroblast growth factor homologous factors (FHFs) bind to the intracellular C-terminal region of the Nav alpha subunit to modulate fast inactivation of the channel. In this study we solved the crystal structure of a 149-residue-long fragment of human FHF2A which unveils the structural features of the homology core domain of all 10 human FHF isoforms. Through analysis of crystal packing contacts and site-directed mutagenesis experiments we identified a conserved surface on the FHF core domain that mediates channel binding in vitro and in vivo. Mutations at this channel binding surface impaired the ability of FHFs to co-localize with Navs at the axon initial segment of hippocampal neurons. The mutations also disabled FHF modulation of voltage-dependent fast inactivation of sodium channels in neuronal cells. Based on our data, we propose that FHFs constitute auxiliary subunits for Navs.

Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channels.,Goetz R, Dover K, Laezza F, Shtraizent N, Huang X, Tchetchik D, Eliseenkova AV, Xu CF, Neubert TA, Ornitz DM, Goldfarb M, Mohammadi M J Biol Chem. 2009 Jun 26;284(26):17883-96. Epub 2009 Apr 30. PMID:19406745^[4]

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

References

↑ Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004 Jul 28;24(30):6765-75. PMID:15282281 doi:10.1523/JNEUROSCI.1628-04.2004
↑ Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004 Jul 28;24(30):6765-75. PMID:15282281 doi:10.1523/JNEUROSCI.1628-04.2004
↑ Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004 Jul 28;24(30):6765-75. PMID:15282281 doi:10.1523/JNEUROSCI.1628-04.2004
↑ Goetz R, Dover K, Laezza F, Shtraizent N, Huang X, Tchetchik D, Eliseenkova AV, Xu CF, Neubert TA, Ornitz DM, Goldfarb M, Mohammadi M. Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channels. J Biol Chem. 2009 Jun 26;284(26):17883-96. Epub 2009 Apr 30. PMID:19406745 doi:https://dx.doi.org/10.1074/jbc.M109.001842

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OCA

[1] Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004 Jul 28;24(30):6765-75. PMID:15282281 doi:10.1523/JNEUROSCI.1628-04.2004

[2] Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004 Jul 28;24(30):6765-75. PMID:15282281 doi:10.1523/JNEUROSCI.1628-04.2004

[3] Wittmack EK, Rush AM, Craner MJ, Goldfarb M, Waxman SG, Dib-Hajj SD. Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons. J Neurosci. 2004 Jul 28;24(30):6765-75. PMID:15282281 doi:10.1523/JNEUROSCI.1628-04.2004

[4] Goetz R, Dover K, Laezza F, Shtraizent N, Huang X, Tchetchik D, Eliseenkova AV, Xu CF, Neubert TA, Ornitz DM, Goldfarb M, Mohammadi M. Crystal structure of a fibroblast growth factor homologous factor (FHF) defines a conserved surface on FHFs for binding and modulation of voltage-gated sodium channels. J Biol Chem. 2009 Jun 26;284(26):17883-96. Epub 2009 Apr 30. PMID:19406745 doi:https://dx.doi.org/10.1074/jbc.M109.001842

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[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='3hbw' size='340' side='right'caption='[[3hbw]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3hbw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HBW FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3hbw]] 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=3HBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HBW FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1q1u|1q1u]]</div></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]] 1.9&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">FGF13, FHF2, fibroblast growth factor homologous factor 2 (FHF2) ([https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3hbw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hbw OCA], [https://pdbe.org/3hbw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hbw RCSB], [https://www.ebi.ac.uk/pdbsum/3hbw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hbw ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/FGF13_HUMAN FGF13_HUMAN]] Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, may participate to the refinement of axons by negatively regulating axonal and leading processes branching. Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus.<ref>PMID:15282281</ref>   May regulate voltage-gated sodium channels transport and function.<ref>PMID:15282281</ref>   May also play a role in MAPK signaling.<ref>PMID:15282281</ref>
+[https://www.uniprot.org/uniprot/FGF13_HUMAN FGF13_HUMAN] Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules. Through its action on microtubules, may participate to the refinement of axons by negatively regulating axonal and leading processes branching. Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus.<ref>PMID:15282281</ref>   May regulate voltage-gated sodium channels transport and function.<ref>PMID:15282281</ref>   May also play a role in MAPK signaling.<ref>PMID:15282281</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Mohammadi, M]]
+[[Category: Mohammadi M]]
-[[Category: Alternative splicing]]
-[[Category: Beta-trefoil fold]]
-[[Category: Growth factor]]
-[[Category: Hormone]]
-[[Category: Polymorphism]]

3hbw: Difference between revisions

Latest revision as of 07:19, 6 September 2023

Crystal Structure of Human Fibroblast Growth Factor Homologous Factor 2A (FHF2A), also referred to as Fibroblast Growth Factor 13A (FGF13A)

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

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