1eku

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /> <applet load="1eku" size="450" color="white" frame="true" align="right" spinBox="true" caption="1eku, resolution 2.9&Aring;" /> '''CRYSTAL STRUCTURE OF...)
Current revision (07:04, 7 February 2024) (edit) (undo)
 
(14 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1eku.gif|left|200px]]<br />
 
-
<applet load="1eku" size="450" color="white" frame="true" align="right" spinBox="true"
 
-
caption="1eku, resolution 2.9&Aring;" />
 
-
'''CRYSTAL STRUCTURE OF A BIOLOGICALLY ACTIVE SINGLE CHAIN MUTANT OF HUMAN IFN-GAMMA'''<br />
 
-
==Overview==
+
==CRYSTAL STRUCTURE OF A BIOLOGICALLY ACTIVE SINGLE CHAIN MUTANT OF HUMAN IFN-GAMMA==
-
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--&gt;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.
+
<StructureSection load='1eku' size='340' side='right'caption='[[1eku]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1eku]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EKU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EKU FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
 +
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1eku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1eku OCA], [https://pdbe.org/1eku PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1eku RCSB], [https://www.ebi.ac.uk/pdbsum/1eku PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1eku ProSAT]</span></td></tr>
 +
</table>
 +
== Disease ==
 +
[https://www.uniprot.org/uniprot/IFNG_HUMAN IFNG_HUMAN] In Caucasians, genetic variation in IFNG is associated with the risk of aplastic anemia (AA) [MIM:[https://omim.org/entry/609135 609135]. AA is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. In most patients, the stem cell lesion is caused by an autoimmune attack. T-lymphocytes, activated by an endogenous or exogenous, and most often unknown antigenic stimulus, secrete cytokines, including IFN-gamma, which would in turn be able to suppress hematopoiesis.
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/IFNG_HUMAN IFNG_HUMAN] Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.
-
==Disease==
+
==See Also==
-
Known diseases associated with this structure: AIDS, rapid progression to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Aplastic anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Hepatitis C virus, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Interferon, immune, deficiency OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], TSC2 angiomyolipomas, renal, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]], Tuberculosis, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147570 147570]]
+
*[[Interferon 3D structures|Interferon 3D structures]]
-
 
+
__TOC__
-
==About this Structure==
+
</StructureSection>
-
1EKU 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 SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EKU 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10860730 10860730]
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
-
[[Category: Single protein]]
+
[[Category: Large Structures]]
-
[[Category: Curry, B.]]
+
[[Category: Curry B]]
-
[[Category: DiGiacomo, R.]]
+
[[Category: DiGiacomo R]]
-
[[Category: Indelicato, S.R.]]
+
[[Category: Indelicato SR]]
-
[[Category: Landar, A.]]
+
[[Category: Landar A]]
-
[[Category: Parker, M.H.]]
+
[[Category: Parker MH]]
-
[[Category: Walter, M.R.]]
+
[[Category: Walter MR]]
-
[[Category: SO4]]
+
-
[[Category: cytokine]]
+
-
[[Category: interferon]]
+
-
[[Category: protein engineering]]
+
-
 
+
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:44:24 2007''
+

Current revision

CRYSTAL STRUCTURE OF A BIOLOGICALLY ACTIVE SINGLE CHAIN MUTANT OF HUMAN IFN-GAMMA

PDB ID 1eku

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1eku"
Personal tools