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1z2m
From Proteopedia
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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 OS4 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
Page seeded by OCA on Mon Nov 12 20:28:36 2007
