1xr0
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1xr0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xr0 OCA], [http://www.ebi.ac.uk/pdbsum/1xr0 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1xr0 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==Overview== | ||
SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the beta sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal beta strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation. | SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the beta sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal beta strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Atopic dermatitis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=135940 135940]], Ichthyosis vulgaris OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=135940 135940]], Jackson-Weiss syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=136350 136350]], Kallmann syndrome 2 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=136350 136350]], Pfeiffer syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=136350 136350]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Zhou, M M.]] | [[Category: Zhou, M M.]] | ||
[[Category: fgfr]] | [[Category: fgfr]] | ||
| - | [[Category: npxpy motif]] | + | [[Category: npxpy motif,]] |
[[Category: phosphotyrosine binding domain]] | [[Category: phosphotyrosine binding domain]] | ||
[[Category: ptb]] | [[Category: ptb]] | ||
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[[Category: trk]] | [[Category: trk]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:53:26 2008'' |
Revision as of 21:53, 30 March 2008
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors
Overview
SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the beta sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal beta strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation.
About this Structure
1XR0 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors., Dhalluin C, Yan KS, Plotnikova O, Lee KW, Zeng L, Kuti M, Mujtaba S, Goldfarb MP, Zhou MM, Mol Cell. 2000 Oct;6(4):921-9. PMID:11090629
Page seeded by OCA on Mon Mar 31 00:53:26 2008
Categories: Homo sapiens | Protein complex | Dhalluin, C. | Goldfarb, M P. | Kuti, M. | Lee, K W. | Mujtaba, S. | Plotnikova, O. | Yan, K S. | Zeng, L. | Zhou, M M. | Fgfr | Npxpy motif, | Phosphotyrosine binding domain | Ptb | Snt | Trk
