1sgh

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(New page: 200px<br /> <applet load="1sgh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1sgh, resolution 3.5&Aring;" /> '''Moesin FERM domain b...)
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'''Moesin FERM domain bound to EBP50 C-terminal peptide'''<br />
'''Moesin FERM domain bound to EBP50 C-terminal peptide'''<br />
==Overview==
==Overview==
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Members of the ezrin-radixin-moesin (ERM) protein family serve as, regulated microfilament-membrane crosslinking proteins that, upon, activation, bind the scaffolding protein ERM-phosphoprotein of 50 kDa, (EBP50). Here we report a 3.5 A resolution diffraction analysis of a, complex between the active moesin N-terminal FERM domain and a 38 residue, peptide from the C terminus of EBP50. This crystallographic result, combined with sequence and structural comparisons, suggests that the, C-terminal 11 residues of EBP50 binds as an alpha-helix at the same site, occupied in the dormant monomer by the last 11 residues of the inhibitory, moesin C-terminal tail. Biochemical support for this interpretation, derives from in vitro studies showing that appropriate mutations in both, the EBP50 tail peptide and the FERM domain reduce binding, and that a, peptide representing just the C-terminal 14 residues of EBP50 also binds, to moesin. Combined with the recent identification of the I-CAM-2 binding, site on the ERM FERM domain (Hamada, K., Shimizu, T., Yonemura, S., Tsukita, S., and Hakoshima, T. (2003) EMBO J. 22, 502-514), this study, reveals that the FERM domain contains two distinct binding sites for, membrane-associated proteins. The contribution of each ligand to ERM, function can now be dissected by making structure-based mutations that, specifically affect the binding of each ligand.
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Members of the ezrin-radixin-moesin (ERM) protein family serve as regulated microfilament-membrane crosslinking proteins that, upon activation, bind the scaffolding protein ERM-phosphoprotein of 50 kDa (EBP50). Here we report a 3.5 A resolution diffraction analysis of a complex between the active moesin N-terminal FERM domain and a 38 residue peptide from the C terminus of EBP50. This crystallographic result, combined with sequence and structural comparisons, suggests that the C-terminal 11 residues of EBP50 binds as an alpha-helix at the same site occupied in the dormant monomer by the last 11 residues of the inhibitory moesin C-terminal tail. Biochemical support for this interpretation derives from in vitro studies showing that appropriate mutations in both the EBP50 tail peptide and the FERM domain reduce binding, and that a peptide representing just the C-terminal 14 residues of EBP50 also binds to moesin. Combined with the recent identification of the I-CAM-2 binding site on the ERM FERM domain (Hamada, K., Shimizu, T., Yonemura, S., Tsukita, S., and Hakoshima, T. (2003) EMBO J. 22, 502-514), this study reveals that the FERM domain contains two distinct binding sites for membrane-associated proteins. The contribution of each ligand to ERM function can now be dissected by making structure-based mutations that specifically affect the binding of each ligand.
==About this Structure==
==About this Structure==
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1SGH 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1SGH OCA].
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1SGH 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=1SGH OCA].
==Reference==
==Reference==
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[[Category: Bretscher, A.]]
[[Category: Bretscher, A.]]
[[Category: Chambers, D.]]
[[Category: Chambers, D.]]
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[[Category: Faber, H.R.]]
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[[Category: Faber, H R.]]
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[[Category: Finnerty, C.M.]]
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[[Category: Finnerty, C M.]]
[[Category: Ingraffea, J.]]
[[Category: Ingraffea, J.]]
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[[Category: Karplus, P.A.]]
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[[Category: Karplus, P A.]]
[[Category: ferm-peptide complex]]
[[Category: ferm-peptide complex]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:13:19 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:01:15 2008''

Revision as of 13:01, 21 February 2008


1sgh, resolution 3.5Å

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Moesin FERM domain bound to EBP50 C-terminal peptide

Overview

Members of the ezrin-radixin-moesin (ERM) protein family serve as regulated microfilament-membrane crosslinking proteins that, upon activation, bind the scaffolding protein ERM-phosphoprotein of 50 kDa (EBP50). Here we report a 3.5 A resolution diffraction analysis of a complex between the active moesin N-terminal FERM domain and a 38 residue peptide from the C terminus of EBP50. This crystallographic result, combined with sequence and structural comparisons, suggests that the C-terminal 11 residues of EBP50 binds as an alpha-helix at the same site occupied in the dormant monomer by the last 11 residues of the inhibitory moesin C-terminal tail. Biochemical support for this interpretation derives from in vitro studies showing that appropriate mutations in both the EBP50 tail peptide and the FERM domain reduce binding, and that a peptide representing just the C-terminal 14 residues of EBP50 also binds to moesin. Combined with the recent identification of the I-CAM-2 binding site on the ERM FERM domain (Hamada, K., Shimizu, T., Yonemura, S., Tsukita, S., and Hakoshima, T. (2003) EMBO J. 22, 502-514), this study reveals that the FERM domain contains two distinct binding sites for membrane-associated proteins. The contribution of each ligand to ERM function can now be dissected by making structure-based mutations that specifically affect the binding of each ligand.

About this Structure

1SGH is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

The EBP50-moesin interaction involves a binding site regulated by direct masking on the FERM domain., Finnerty CM, Chambers D, Ingraffea J, Faber HR, Karplus PA, Bretscher A, J Cell Sci. 2004 Mar 15;117(Pt 8):1547-52. PMID:15020681

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