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| | {{STRUCTURE_1eku| PDB=1eku | SCENE= }} | | {{STRUCTURE_1eku| PDB=1eku | SCENE= }} |
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| - | '''CRYSTAL STRUCTURE OF A BIOLOGICALLY ACTIVE SINGLE CHAIN MUTANT OF HUMAN IFN-GAMMA'''
| + | ===CRYSTAL STRUCTURE OF A BIOLOGICALLY ACTIVE SINGLE CHAIN MUTANT OF HUMAN IFN-GAMMA=== |
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| - | ==Overview==
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| - | A mutant form of human interferon-gamma (IFN-gamma SC1) that binds one IFN-gamma receptor alpha chain (IFN-gamma R alpha) has been designed and characterized. IFN-gamma SC1 was derived by linking the two peptide chains of the IFN-gamma dimer by a seven-residue linker and changing His111 in the first chain to an aspartic acid residue. Isothermal titration calorimetry shows that IFN-gamma SC1 forms a 1:1 complex with its high-affinity receptor (IFN-gamma R alpha) with an affinity of 27(+/- 9) nM. The crystal structure of IFN-gamma SC1 has been determined at 2.9 A resolution from crystals grown in 1.4 M citrate solutions at pH 7.6. Comparison of the wild-type receptor-binding domain and the Asp111-containing domain of IFN-gamma SC1 show that they are structurally equivalent but have very different electrostatic surface potentials. As a result, surface charge rather than structural changes is likely responsible for the inability of the His111-->Asp domain of to bind IFN-gamma R alpha. The AB loops of IFN-gamma SC1 adopt conformations similar to the ordered loops of IFN-gamma observed in the crystal structure of the IFN-gamma/IFN-gamma R alpha complex. Thus, IFN-gamma R alpha binding does not result in a large conformational change in the AB loop as previously suggested. The structure also reveals the final six C-terminal amino acid residues of IFN-gamma SC1 (residues 253-258) that have not been observed in any other reported IFN-gamma structures. Despite binding to only one IFN-gamma R alpha, IFN-gamma SC1 is biologically active in cell proliferation, MHC class I induction, and anti-viral assays. This suggests that one domain of IFN-gamma is sufficient to recruit IFN-gamma R alpha and IFN-gamma R beta into a complex competent for eliciting biological activity. The current data are consistent with the main role of the IFN-gamma dimer being to decrease the dissociation constant of IFN-gamma for its cellular receptors.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_10860730}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 10860730 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_10860730}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Interferon]] | | [[Category: Interferon]] |
| | [[Category: Protein engineering]] | | [[Category: Protein engineering]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 15:13:23 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 00:54:33 2008'' |
Revision as of 21:54, 30 June 2008
Template:STRUCTURE 1eku
CRYSTAL STRUCTURE OF A BIOLOGICALLY ACTIVE SINGLE CHAIN MUTANT OF HUMAN IFN-GAMMA
Template:ABSTRACT PUBMED 10860730
About this Structure
1EKU is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Design, characterization, and structure of a biologically active single-chain mutant of human IFN-gamma., Landar A, Curry B, Parker MH, DiGiacomo R, Indelicato SR, Nagabhushan TL, Rizzi G, Walter MR, J Mol Biol. 2000 May 26;299(1):169-79. PMID:10860730
Page seeded by OCA on Tue Jul 1 00:54:33 2008
