1z2m
From Proteopedia
(New page: 200px<br /> <applet load="1z2m" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z2m, resolution 2.50Å" /> '''Crystal Structure o...) |
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| - | [[Image:1z2m.gif|left|200px]]<br /> | + | [[Image:1z2m.gif|left|200px]]<br /><applet load="1z2m" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1z2m" size=" | + | |
caption="1z2m, resolution 2.50Å" /> | caption="1z2m, resolution 2.50Å" /> | ||
'''Crystal Structure of ISG15, the Interferon-Induced Ubiquitin Cross Reactive Protein'''<br /> | '''Crystal Structure of ISG15, the Interferon-Induced Ubiquitin Cross Reactive Protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The biological effects of the ISG15 protein arise in part from its | + | The biological effects of the ISG15 protein arise in part from its conjugation to cellular targets as a primary response to interferon-alpha/beta induction and other markers of viral or parasitic infection. Recombinant full-length ISG15 has been produced for the first time in high yield by mutating Cys78 to stabilize the protein and by cloning in a C-terminal arginine cap to protect the C terminus against proteolytic inactivation. The cap is subsequently removed with carboxypeptidase B to yield mature biologically active ISG15 capable of stoichiometric ATP-dependent thiolester formation with its human UbE1L activating enzyme. The three-dimensional structure of recombinant ISG15C78S was determined at 2.4-A resolution. The ISG15 structure comprises two beta-grasp folds having main chain root mean square deviation (r.m.s.d.) values from ubiquitin of 1.7 A (N-terminal) and 1.0 A (C-terminal). The beta-grasp domains pack across two conserved 3(10) helices to bury 627 A2 that accounts for 7% of the total solvent-accessible surface area. The distribution of ISG15 surface charge forms a ridge of negative charge extending nearly the full-length of the molecule. Additionally, the N-terminal domain contains an apolar region comprising almost half its solvent accessible surface. The C-terminal domain of ISG15 was superimposed on the structure of Nedd8 (r.m.s.d. = 0.84 A) bound to its AppBp1-Uba3 activating enzyme to model ISG15 binding to UbE1L. The docking model predicts several key side-chain interactions that presumably define the specificity between the ubiquitin and ISG15 ligation pathways to maintain functional integrity of their signaling. |
==About this Structure== | ==About this Structure== | ||
| - | 1Z2M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with OS4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1Z2M is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=OS4:'>OS4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z2M OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Fu, Z.]] | [[Category: Fu, Z.]] | ||
| - | [[Category: Haas, A | + | [[Category: Haas, A L.]] |
| - | [[Category: Kim, J | + | [[Category: Kim, J J.]] |
| - | [[Category: Klein, J | + | [[Category: Klein, J M.]] |
[[Category: Narasimhan, J.]] | [[Category: Narasimhan, J.]] | ||
[[Category: Wang, M.]] | [[Category: Wang, M.]] | ||
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[[Category: ubiquitin cross reactive protein]] | [[Category: ubiquitin cross reactive protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:11:32 2008'' |
Revision as of 14:11, 21 February 2008
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Crystal Structure of ISG15, the Interferon-Induced Ubiquitin Cross Reactive Protein
Overview
The biological effects of the ISG15 protein arise in part from its conjugation to cellular targets as a primary response to interferon-alpha/beta induction and other markers of viral or parasitic infection. Recombinant full-length ISG15 has been produced for the first time in high yield by mutating Cys78 to stabilize the protein and by cloning in a C-terminal arginine cap to protect the C terminus against proteolytic inactivation. The cap is subsequently removed with carboxypeptidase B to yield mature biologically active ISG15 capable of stoichiometric ATP-dependent thiolester formation with its human UbE1L activating enzyme. The three-dimensional structure of recombinant ISG15C78S was determined at 2.4-A resolution. The ISG15 structure comprises two beta-grasp folds having main chain root mean square deviation (r.m.s.d.) values from ubiquitin of 1.7 A (N-terminal) and 1.0 A (C-terminal). The beta-grasp domains pack across two conserved 3(10) helices to bury 627 A2 that accounts for 7% of the total solvent-accessible surface area. The distribution of ISG15 surface charge forms a ridge of negative charge extending nearly the full-length of the molecule. Additionally, the N-terminal domain contains an apolar region comprising almost half its solvent accessible surface. The C-terminal domain of ISG15 was superimposed on the structure of Nedd8 (r.m.s.d. = 0.84 A) bound to its AppBp1-Uba3 activating enzyme to model ISG15 binding to UbE1L. The docking model predicts several key side-chain interactions that presumably define the specificity between the ubiquitin and ISG15 ligation pathways to maintain functional integrity of their signaling.
About this Structure
1Z2M is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of the interferon-induced ubiquitin-like protein ISG15., Narasimhan J, Wang M, Fu Z, Klein JM, Haas AL, Kim JJ, J Biol Chem. 2005 Jul 22;280(29):27356-65. Epub 2005 May 24. PMID:15917233
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