1xr0
From Proteopedia
(New page: 200px<br /> <applet load="1xr0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xr0" /> '''Structural Basis of SNT PTB Domain Interact...) |
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'''Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors'''<br /> | '''Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors'''<br /> | ||
==Overview== | ==Overview== | ||
| - | SNT adaptor proteins transduce activation of fibroblast growth factor | + | 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. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1XR0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1XR0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences 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=1XR0 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Dhalluin, C.]] | [[Category: Dhalluin, C.]] | ||
| - | [[Category: Goldfarb, M | + | [[Category: Goldfarb, M P.]] |
[[Category: Kuti, M.]] | [[Category: Kuti, M.]] | ||
| - | [[Category: Lee, K | + | [[Category: Lee, K W.]] |
[[Category: Mujtaba, S.]] | [[Category: Mujtaba, S.]] | ||
[[Category: Plotnikova, O.]] | [[Category: Plotnikova, O.]] | ||
| - | [[Category: Yan, K | + | [[Category: Yan, K S.]] |
[[Category: Zeng, L.]] | [[Category: Zeng, L.]] | ||
| - | [[Category: Zhou, M | + | [[Category: Zhou, M M.]] |
[[Category: fgfr]] | [[Category: fgfr]] | ||
[[Category: npxpy motif]] | [[Category: npxpy motif]] | ||
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[[Category: trk]] | [[Category: trk]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:57:43 2008'' |
Revision as of 13:57, 21 February 2008
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Structural Basis of SNT PTB Domain Interactions with Distinct Neurotrophic Receptors
Contents |
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.
Disease
Known diseases associated with this structure: Atopic dermatitis, susceptibility to OMIM:[135940], Ichthyosis vulgaris OMIM:[135940], Jackson-Weiss syndrome OMIM:[136350], Kallmann syndrome 2 OMIM:[136350], Pfeiffer syndrome OMIM:[136350]
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 Thu Feb 21 15:57:43 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
