1f1w: Difference between revisions
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New page: left|200px<br /><applet load="1f1w" size="450" color="white" frame="true" align="right" spinBox="true" caption="1f1w, resolution 2.10Å" /> '''SRC SH2 THREF1TRP MU... |
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[[Image:1f1w.gif|left|200px]]<br /><applet load="1f1w" size=" | [[Image:1f1w.gif|left|200px]]<br /><applet load="1f1w" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1f1w, resolution 2.10Å" /> | caption="1f1w, resolution 2.10Å" /> | ||
'''SRC SH2 THREF1TRP MUTANT COMPLEXED WITH THE PHOSPHOPEPTIDE S(PTR)VNVQN'''<br /> | '''SRC SH2 THREF1TRP MUTANT COMPLEXED WITH THE PHOSPHOPEPTIDE S(PTR)VNVQN'''<br /> | ||
==Overview== | ==Overview== | ||
The Src SH2 domain binds pYEEI-containing phosphopeptides in an extended | The Src SH2 domain binds pYEEI-containing phosphopeptides in an extended conformation with a hydrophobic pocket, which includes ThrEF1, binding Ile(pY +3). Mutating ThrEF1 to tryptophan switches specificity to an Asn(pY +2) requirement, yielding a biological mimic of the Grb2 SH2 domain. Here we show that the Src ThrEF1Trp SH2 domain mutant binds pYVNV phosphopeptides in a beta turn conformation, which, despite differing conformations of the interacting tryptophan, closely resembles the native Grb2/pYVNV cognate peptide binding mode. The ThrEF1Trp substitution therefore switches specificity by physically occluding the pTyr +3 binding pocket and by providing additional interaction surface area for Asn(pY +2). This demonstrates structurally how novel SH2 domain specificities may rapidly evolve through single amino acid substitutions and suggests how new signaling pathways may develop. | ||
==About this Structure== | ==About this Structure== | ||
1F1W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http:// | 1F1W is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Active as [http://en.wikipedia.org/wiki/Transferase Transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 and 2.7.10.2 2.7.10.1 and 2.7.10.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1F1W OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
[[Category: Cunningham, A | [[Category: Cunningham, A M.]] | ||
[[Category: Gish, G | [[Category: Gish, G D.]] | ||
[[Category: Kimber, M | [[Category: Kimber, M S.]] | ||
[[Category: Nachman, J.]] | [[Category: Nachman, J.]] | ||
[[Category: Pai, E | [[Category: Pai, E F.]] | ||
[[Category: Pawson, T.]] | [[Category: Pawson, T.]] | ||
[[Category: phosphopeptide]] | [[Category: phosphopeptide]] | ||
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[[Category: src]] | [[Category: src]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:33:53 2008'' | ||
