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| - | [[Image:1vet.gif|left|200px]] | |
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| - | <!-- | + | ==Crystal Structure of p14/MP1 at 1.9 A resolution== |
| - | The line below this paragraph, containing "STRUCTURE_1vet", creates the "Structure Box" on the page.
| + | <StructureSection load='1vet' size='340' side='right'caption='[[1vet]], [[Resolution|resolution]] 1.90Å' 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'>[[1vet]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VET OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1VET 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">X-ray diffraction, [[Resolution|Resolution]] 1.9Å</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=1vet FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1vet OCA], [https://pdbe.org/1vet PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1vet RCSB], [https://www.ebi.ac.uk/pdbsum/1vet PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1vet ProSAT]</span></td></tr> |
| - | {{STRUCTURE_1vet| PDB=1vet | SCENE= }}
| + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LTOR3_MOUSE LTOR3_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> <ref>PMID:9733512</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/ve/1vet_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=1vet ConSurf]. |
| | + | <div style="clear:both"></div> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Signaling pathways in eukaryotic cells are often controlled by the formation of specific signaling complexes, which are coordinated by scaffold and adaptor proteins. Elucidating their molecular architecture is essential to understand the spatial and temporal regulation of cellular signaling. p14 and MP1 form a tight (K(d) = 12.8 nM) endosomal adaptor/scaffold complex, which regulates mitogen-activated protein kinase (MAPK) signaling. Here, we present the 1.9-A crystal structure of a biologically functional p14/MP1 complex. The overall topology of the individual MP1 and p14 proteins is almost identical, having a central five-stranded beta-sheet sandwiched between a two-helix and a one-helix layer. Formation of the p14/MP1 heterodimer proceeds by beta-sheet augmentation and yields a unique, almost symmetrical, complex with several potential protein-binding sites on its surface. Mutational analysis allowed identification of the p14 endosomal adaptor motif, which seems to orient the complex relative to the endosomal membrane. Two highly conserved and hydrophobic protein-binding sites are located on the opposite "cytoplasmic" face of the p14/MP1 heterodimer and might therefore function as docking sites for the target proteins extracellular regulated kinase (ERK) 1 and MAPK/ERK kinase 1. Furthermore, detailed sequence analyses revealed that MP1/p14, together with profilins, define a protein superfamily of small subcellular adaptor proteins, named ProflAP. Taken together, the presented work provides insight into the spatial regulation of MAPK signaling, illustrating how p14 and MP1 collaborate as an endosomal adaptor/scaffold complex. |
| | | | |
| - | '''Crystal Structure of p14/MP1 at 1.9 A resolution'''
| + | Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes.,Kurzbauer R, Teis D, de Araujo ME, Maurer-Stroh S, Eisenhaber F, Bourenkov GP, Bartunik HD, Hekman M, Rapp UR, Huber LA, Clausen T Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10984-9. Epub 2004 Jul 19. PMID:15263099<ref>PMID:15263099</ref> |
| - | | + | |
| - | | + | |
| - | ==Overview==
| + | |
| - | Signaling pathways in eukaryotic cells are often controlled by the formation of specific signaling complexes, which are coordinated by scaffold and adaptor proteins. Elucidating their molecular architecture is essential to understand the spatial and temporal regulation of cellular signaling. p14 and MP1 form a tight (K(d) = 12.8 nM) endosomal adaptor/scaffold complex, which regulates mitogen-activated protein kinase (MAPK) signaling. Here, we present the 1.9-A crystal structure of a biologically functional p14/MP1 complex. The overall topology of the individual MP1 and p14 proteins is almost identical, having a central five-stranded beta-sheet sandwiched between a two-helix and a one-helix layer. Formation of the p14/MP1 heterodimer proceeds by beta-sheet augmentation and yields a unique, almost symmetrical, complex with several potential protein-binding sites on its surface. Mutational analysis allowed identification of the p14 endosomal adaptor motif, which seems to orient the complex relative to the endosomal membrane. Two highly conserved and hydrophobic protein-binding sites are located on the opposite "cytoplasmic" face of the p14/MP1 heterodimer and might therefore function as docking sites for the target proteins extracellular regulated kinase (ERK) 1 and MAPK/ERK kinase 1. Furthermore, detailed sequence analyses revealed that MP1/p14, together with profilins, define a protein superfamily of small subcellular adaptor proteins, named ProflAP. Taken together, the presented work provides insight into the spatial regulation of MAPK signaling, illustrating how p14 and MP1 collaborate as an endosomal adaptor/scaffold complex.
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | 1VET is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VET OCA].
| + | </div> |
| | + | <div class="pdbe-citations 1vet" style="background-color:#fffaf0;"></div> |
| | | | |
| - | ==Reference== | + | ==See Also== |
| - | Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes., Kurzbauer R, Teis D, de Araujo ME, Maurer-Stroh S, Eisenhaber F, Bourenkov GP, Bartunik HD, Hekman M, Rapp UR, Huber LA, Clausen T, Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10984-9. Epub 2004 Jul 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15263099 15263099]
| + | *[[Mitogen-activated protein kinase kinase 3D structures|Mitogen-activated protein kinase kinase 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Protein complex]]
| + | [[Category: Bartunik HD]] |
| - | [[Category: Bartunik, H D.]] | + | [[Category: Bourenkov GP]] |
| - | [[Category: Bourenkov, G P.]] | + | [[Category: Clausen T]] |
| - | [[Category: Clausen, T.]] | + | [[Category: Eisenhaber F]] |
| - | [[Category: Eisenhaber, F.]] | + | [[Category: Hekman M]] |
| - | [[Category: Hekman, M.]] | + | [[Category: Huber LA]] |
| - | [[Category: Huber, L A.]] | + | [[Category: Kurzbauer R]] |
| - | [[Category: Kurzbauer, R.]] | + | [[Category: Maurer-Stroh S]] |
| - | [[Category: Maurer-Stroh, S.]] | + | [[Category: Teis D]] |
| - | [[Category: Teis, D.]] | + | |
| - | [[Category: Adaptor]]
| + | |
| - | [[Category: Profilin]]
| + | |
| - | [[Category: Scaffold]]
| + | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 12:27:37 2008''
| + | |
| Structural highlights
Function
LTOR3_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] [2]
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
Signaling pathways in eukaryotic cells are often controlled by the formation of specific signaling complexes, which are coordinated by scaffold and adaptor proteins. Elucidating their molecular architecture is essential to understand the spatial and temporal regulation of cellular signaling. p14 and MP1 form a tight (K(d) = 12.8 nM) endosomal adaptor/scaffold complex, which regulates mitogen-activated protein kinase (MAPK) signaling. Here, we present the 1.9-A crystal structure of a biologically functional p14/MP1 complex. The overall topology of the individual MP1 and p14 proteins is almost identical, having a central five-stranded beta-sheet sandwiched between a two-helix and a one-helix layer. Formation of the p14/MP1 heterodimer proceeds by beta-sheet augmentation and yields a unique, almost symmetrical, complex with several potential protein-binding sites on its surface. Mutational analysis allowed identification of the p14 endosomal adaptor motif, which seems to orient the complex relative to the endosomal membrane. Two highly conserved and hydrophobic protein-binding sites are located on the opposite "cytoplasmic" face of the p14/MP1 heterodimer and might therefore function as docking sites for the target proteins extracellular regulated kinase (ERK) 1 and MAPK/ERK kinase 1. Furthermore, detailed sequence analyses revealed that MP1/p14, together with profilins, define a protein superfamily of small subcellular adaptor proteins, named ProflAP. Taken together, the presented work provides insight into the spatial regulation of MAPK signaling, illustrating how p14 and MP1 collaborate as an endosomal adaptor/scaffold complex.
Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes.,Kurzbauer R, Teis D, de Araujo ME, Maurer-Stroh S, Eisenhaber F, Bourenkov GP, Bartunik HD, Hekman M, Rapp UR, Huber LA, Clausen T Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):10984-9. Epub 2004 Jul 19. PMID:15263099[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Schaeffer HJ, Catling AD, Eblen ST, Collier LS, Krauss A, Weber MJ. MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science. 1998 Sep 11;281(5383):1668-71. PMID:9733512
- ↑ 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
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