3mxc

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{{STRUCTURE_3mxc| PDB=3mxc | SCENE= }}
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==Structures of Grb2-SH2 Domain and AICD peptide Complexes Reveal a Conformational Switch and Their Functional Implications.==
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===Structures of Grb2-SH2 Domain and AICD peptide Complexes Reveal a Conformational Switch and Their Functional Implications.===
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<StructureSection load='3mxc' size='340' side='right' caption='[[3mxc]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_22001015}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3mxc]] is a 2 chain structure with 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=3MXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3MXC FirstGlance]. <br>
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</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3mxy|3mxy]], [[3kfj|3kfj]], [[1jyr|1jyr]], [[1jyq|1jyq]]</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GRB2, ASH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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=3mxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mxc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3mxc RCSB], [http://www.ebi.ac.uk/pdbsum/3mxc PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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It has been hypothesized previously that synergistic effect of both amyloid precursor protein intracellular C-terminal domain (AICD) and Abeta aggregation could contribute to Alzheimer's disease pathogenesis. Structural studies of AICD have found no stable globular fold over a broad range of pH. Present work is based on the premises that a conformational switch involving the flipping of C-terminal helix of AICD would be essential for effective binding with the Src homology 2 (SH2) domain of growth factor receptor binding protein-2 (Grb2) and subsequent initiation of Grb2-mediated endo-lysosomal pathway. High-resolution crystal structures of Grb2-SH2 domain bound to AICD peptides reveal a unique mode of binding where the peptides assume a noncanonical conformation that is unlike other structures of AICD peptides bound to protein-tyrosine-binding domains or that of its free state; rather, a flipping of the C-terminal helix of AICD is evident. The involvement of different AICD residues in Grb2-SH2 interaction is further elucidated through fluorescence-based assays. Our results reveal the significance of a specific interaction of the two molecules to optimize the rapid transport of AICD inside endosomal vesicles presumably to reduce the cytotoxic load.
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==Function==
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Functional Implications of the Conformational Switch in AICD Peptide upon Binding to Grb2-SH2 Domain.,Das S, Raychaudhuri M, Sen U, Mukhopadhyay D J Mol Biol. 2011 Oct 4. PMID:22001015<ref>PMID:22001015</ref>
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[[http://www.uniprot.org/uniprot/GRB2_HUMAN GRB2_HUMAN]] Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.<ref>PMID:1322798</ref><ref>PMID:8178156</ref><ref>PMID:19815557</ref> Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death.<ref>PMID:1322798</ref><ref>PMID:8178156</ref><ref>PMID:19815557</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3mxc]] is a 2 chain structure with 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=3MXC OCA].
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</div>
==See Also==
==See Also==
*[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]]
*[[Growth factor receptor-bound protein|Growth factor receptor-bound protein]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:022001015</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Das, S.]]
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[[Category: Das, S]]
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[[Category: Sen, U.]]
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[[Category: Sen, U]]
[[Category: Aicd]]
[[Category: Aicd]]
[[Category: Alzheimer's disease]]
[[Category: Alzheimer's disease]]

Revision as of 15:31, 18 December 2014

Structures of Grb2-SH2 Domain and AICD peptide Complexes Reveal a Conformational Switch and Their Functional Implications.

3mxc, resolution 2.00Å

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