|
|
| (11 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| - | [[Image:1pfl.gif|left|200px]] | |
| | | | |
| - | <!-- | + | ==REFINED SOLUTION STRUCTURE OF HUMAN PROFILIN I== |
| - | The line below this paragraph, containing "STRUCTURE_1pfl", creates the "Structure Box" on the page.
| + | <StructureSection load='1pfl' size='340' side='right'caption='[[1pfl]]' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[1pfl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PFL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PFL FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1pfl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pfl OCA], [https://pdbe.org/1pfl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pfl RCSB], [https://www.ebi.ac.uk/pdbsum/1pfl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pfl ProSAT]</span></td></tr> |
| - | {{STRUCTURE_1pfl| PDB=1pfl | SCENE= }}
| + | </table> |
| | + | == Disease == |
| | + | [https://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN] Defects in PFN1 are the cause of amyotrophic lateral sclerosis 18 (ALS18) [MIM:[https://omim.org/entry/614808 614808]. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.<ref>PMID:22801503</ref> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/PROF1_HUMAN PROF1_HUMAN] Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.<ref>PMID:18573880</ref> |
| | + | == Evolutionary Conservation == |
| | + | [[Image:Consurf_key_small.gif|200px|right]] |
| | + | Check<jmol> |
| | + | <jmolCheckbox> |
| | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pf/1pfl_consurf.spt"</scriptWhenChecked> |
| | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | + | <text>to colour the structure by Evolutionary Conservation</text> |
| | + | </jmolCheckbox> |
| | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1pfl ConSurf]. |
| | + | <div style="clear:both"></div> |
| | | | |
| - | '''REFINED SOLUTION STRUCTURE OF HUMAN PROFILIN I'''
| + | ==See Also== |
| - | | + | *[[Profilin 3D Structures|Profilin 3D Structures]] |
| - | | + | == References == |
| - | ==Overview== | + | <references/> |
| - | Profilin is a ubiquitous eukaryotic protein that binds to both cytosolic actin and the phospholipid phosphatidylinositol-4,5-bisphosphate. These dual competitive binding capabilities of profilin suggest that profilin serves as a link between the phosphatidyl inositol cycle and actin polymerization, and thus profilin may be an essential component in the signaling pathway leading to cytoskeletal rearrangement. The refined three-dimensional solution structure of human profilin I has been determined using multidimensional heteronuclear NMR spectroscopy. Twenty structures were selected to represent the solution conformational ensemble. This ensemble of structures has root-mean-square distance deviations from the mean structure of 0.58 A for the backbone atoms and 0.98 A for all non-hydrogen atoms. Comparison of the solution structure of human profilin to the crystal structure of bovine profilin reveals that, although profilin adopts essentially identical conformations in both states, the solution structure is more compact than the crystal structure. Interestingly, the regions that show the most structural diversity are located at or near the actin-binding site of profilin. We suggest that structural differences are reflective of dynamical properties of profilin that facilitate favorable interactions with actin. The global folding pattern of human profilin also closely resembles that of Acanthamoeba profilin I, reflective of the 22% sequence identity and approximately 45% sequence similarity between these two proteins.
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure==
| + | |
| - | 1PFL is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PFL OCA].
| + | |
| - | | + | |
| - | ==Reference== | + | |
| - | Refined solution structure of human profilin I., Metzler WJ, Farmer BT 2nd, Constantine KL, Friedrichs MS, Lavoie T, Mueller L, Protein Sci. 1995 Mar;4(3):450-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7795529 7795529]
| + | |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Single protein]] | + | [[Category: Large Structures]] |
| - | [[Category: Constantine, K L.]] | + | [[Category: Constantine KL]] |
| - | [[Category: Friedrichs, M S.]] | + | [[Category: Farmer II BT]] |
| - | [[Category: II, B T.Farmer.]] | + | [[Category: Friedrichs MS]] |
| - | [[Category: Lavoie, T.]] | + | [[Category: Lavoie T]] |
| - | [[Category: Metzler, W J.]] | + | [[Category: Metzler WJ]] |
| - | [[Category: Mueller, L.]] | + | [[Category: Mueller L]] |
| - | [[Category: Regulatory protein]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:01:47 2008''
| + | |
| Structural highlights
Disease
PROF1_HUMAN Defects in PFN1 are the cause of amyotrophic lateral sclerosis 18 (ALS18) [MIM:614808. A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases.[1]
Function
PROF1_HUMAN Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
See Also
References
- ↑ Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, van den Berg LH, Glass JD, Siciliano G, Cirulli ET, Goldstein DB, Salachas F, Meininger V, Rossoll W, Ratti A, Gellera C, Bosco DA, Bassell GJ, Silani V, Drory VE, Brown RH Jr, Landers JE. Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis. Nature. 2012 Aug 23;488(7412):499-503. doi: 10.1038/nature11280. PMID:22801503 doi:10.1038/nature11280
- ↑ Shao J, Welch WJ, Diprospero NA, Diamond MI. Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation. Mol Cell Biol. 2008 Sep;28(17):5196-208. doi: 10.1128/MCB.00079-08. Epub 2008 Jun, 23. PMID:18573880 doi:10.1128/MCB.00079-08
|
