High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.
Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3787023?pdf=render |
| _version_ | 1818695051357716480 |
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| author | Kunitake Higo Teikichi Ikura Masayuki Oda Hisayuki Morii Jun Takahashi Ryo Abe Nobutoshi Ito |
| author_facet | Kunitake Higo Teikichi Ikura Masayuki Oda Hisayuki Morii Jun Takahashi Ryo Abe Nobutoshi Ito |
| author_sort | Kunitake Higo |
| collection | DOAJ |
| description | Src homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation. |
| first_indexed | 2024-12-17T13:39:19Z |
| format | Article |
| id | doaj.art-80d8e7e84a41461aa9a0f8041fbc5118 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T13:39:19Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-80d8e7e84a41461aa9a0f8041fbc51182022-12-21T21:46:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0189e7448210.1371/journal.pone.0074482High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28.Kunitake HigoTeikichi IkuraMasayuki OdaHisayuki MoriiJun TakahashiRyo AbeNobutoshi ItoSrc homology 2 (SH2) domains play a critical role in cellular signal transduction. They bind to peptides containing phosphotyrosine (pY) with various specificities that depend on the flanking amino-acid residues. The SH2 domain of growth-factor receptor-bound protein 2 (Grb2) specifically recognizes pY-X-N-X, whereas the SH2 domains in phosphatidylinositol 3-kinase (PI3K) recognize pY-X-X-M. Binding of the pY site in CD28 (pY-M-N-M) by PI3K and Grb2 through their SH2 domains is a key step that triggers the CD28 signal transduction for T cell activation and differentiation. In this study, we determined the crystal structure of the Grb2 SH2 domain in complex with a pY-containing peptide derived from CD28 at 1.35 Å resolution. The peptide was found to adopt a twisted U-type conformation, similar to, but distinct from type-I β-turn. In all previously reported crystal structures, the peptide bound to the Grb2 SH2 domains adopts a type-I β-turn conformation, except those with a proline residue at the pY+3 position. Molecular modeling also suggests that the same peptide bound to PI3K might adopt a very different conformation.http://europepmc.org/articles/PMC3787023?pdf=render |
| spellingShingle | Kunitake Higo Teikichi Ikura Masayuki Oda Hisayuki Morii Jun Takahashi Ryo Abe Nobutoshi Ito High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. PLoS ONE |
| title | High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. |
| title_full | High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. |
| title_fullStr | High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. |
| title_full_unstemmed | High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. |
| title_short | High resolution crystal structure of the Grb2 SH2 domain with a phosphopeptide derived from CD28. |
| title_sort | high resolution crystal structure of the grb2 sh2 domain with a phosphopeptide derived from cd28 |
| url | http://europepmc.org/articles/PMC3787023?pdf=render |
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