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| | ==Structure of the Adaptor Protein p14 reveals a Profilin-like Fold with Novel Function== | | ==Structure of the Adaptor Protein p14 reveals a Profilin-like Fold with Novel Function== |
| - | <StructureSection load='1szv' size='340' side='right' caption='[[1szv]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='1szv' size='340' side='right'caption='[[1szv]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1szv]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SZV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1SZV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1szv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SZV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1SZV FirstGlance]. <br> |
| - | </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=1szv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1szv OCA], [http://pdbe.org/1szv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1szv RCSB], [http://www.ebi.ac.uk/pdbsum/1szv PDBsum]</span></td></tr> | + | </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=1szv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1szv OCA], [https://pdbe.org/1szv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1szv RCSB], [https://www.ebi.ac.uk/pdbsum/1szv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1szv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LTOR2_MOUSE LTOR2_MOUSE]] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.<ref>PMID:15263099</ref> | + | [https://www.uniprot.org/uniprot/LTOR2_MOUSE LTOR2_MOUSE] As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.<ref>PMID:15263099</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sz/1szv_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/sz/1szv_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Farooq, A]] | + | [[Category: Mus musculus]] |
| - | [[Category: Qian, C]] | + | [[Category: Farooq A]] |
| - | [[Category: Wang, X]] | + | [[Category: Qian C]] |
| - | [[Category: Zeng, L]] | + | [[Category: Wang X]] |
| - | [[Category: Zhang, Q]] | + | [[Category: Zeng L]] |
| - | [[Category: Zhou, M M]] | + | [[Category: Zhang Q]] |
| - | [[Category: P14]]
| + | [[Category: Zhou MM]] |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
LTOR2_MOUSE As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator functions as a guanine nucleotide exchange factor activating the small GTPases Rag. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. Adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2.[1]
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
The adaptor protein p14 is associated with the cytoplasmic face of late endosomes that is involved in cell-surface receptor endocytosis and it also directly interacts with MP1, a scaffolding protein that binds the MAP kinase ERK1 and its upstream kinase activator MEK1. The interaction of p14 with MP1 recruits the latter to late endosomes and the endosomal localization of p14/MP1-MEK1-ERK1 scaffolding complex is required for signaling via ERK MAP kinase in an efficient and specific manner upon receptor stimulation. Here, we report the three-dimensional solution structure of the adaptor protein p14. The structure reveals a profilin-like fold with a central five-stranded beta-sheet sandwiched between alpha-helices. Unlike profilin, however, p14 exhibits weak interaction with selective phosphoinositides but no affinity towards proline-rich sequences. Structural comparison between profilin and p14 reveals the molecular basis for the differences in these functions. We further mapped the MP1 binding sites on p14 by NMR, and discuss the implications of these important findings on the possible function of p14.
Structure of the adaptor protein p14 reveals a profilin-like fold with distinct function.,Qian C, Zhang Q, Wang X, Zeng L, Farooq A, Zhou MM J Mol Biol. 2005 Mar 25;347(2):309-21. Epub 2005 Jan 27. PMID:15740743[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kurzbauer R, Teis D, de Araujo ME, Maurer-Stroh S, Eisenhaber F, Bourenkov GP, Bartunik HD, Hekman M, Rapp UR, Huber LA, Clausen T. Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes. Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10984-9. Epub 2004 Jul 19. PMID:15263099 doi:10.1073/pnas.0403435101
- ↑ Qian C, Zhang Q, Wang X, Zeng L, Farooq A, Zhou MM. Structure of the adaptor protein p14 reveals a profilin-like fold with distinct function. J Mol Biol. 2005 Mar 25;347(2):309-21. Epub 2005 Jan 27. PMID:15740743 doi:http://dx.doi.org/10.1016/j.jmb.2005.01.031
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