View source for 2kz1


==Inter-molecular interactions in a 44 kDa interferon-receptor complex detected by asymmetric back-protonation and 2D NOESY==
<StructureSection load='2kz1' size='340' side='right'caption='[[2kz1]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2kz1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ksx 2ksx]. The August 2010 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Interferons''  by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2010_8 10.2210/rcsb_pdb/mom_2010_8]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KZ1 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IFNA2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IFNABR ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2kz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kz1 OCA], [https://pdbe.org/2kz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kz1 RCSB], [https://www.ebi.ac.uk/pdbsum/2kz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kz1 ProSAT]</span></td></tr>
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== Function ==
[[https://www.uniprot.org/uniprot/IFNA2_HUMAN IFNA2_HUMAN]] Produced by macrophages, IFN-alpha have antiviral activities. [[https://www.uniprot.org/uniprot/INAR2_HUMAN INAR2_HUMAN]] Associates with IFNAR1 to form the type I interferon receptor. Receptor for interferons alpha and beta. Involved in IFN-mediated STAT1, STAT2 and STAT3 activation. Isoform 1 and isoform 2 are directly involved in signal transduction due to their association with the TYR kinase, JAK1. Isoform 3 is a potent inhibitor of type I IFN receptor activity.<ref>PMID:8181059</ref> <ref>PMID:7665574</ref> <ref>PMID:7759950</ref> <ref>PMID:11682488</ref> <ref>PMID:12105218</ref>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kz/2kz1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2kz1 ConSurf].
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== Publication Abstract from PubMed ==
Type I interferons (IFNs) make up a family of homologous helical cytokines initiating strong antiviral and antiproliferative activity. All type I IFNs bind to a common cell surface receptor consisting of two subunits, IFNAR1 and IFNAR2, associating upon binding of interferon. We studied intermolecular interactions between IFNAR2-EC and IFNalpha2 using asymmetric reverse-protonation of the different complex components and two-dimensional homonuclear NOESY. This new approach revealed with an excellent signal-to-noise ratio 24 new intermolecular NOEs between the two molecules despite the low concentration of the complex (0.25 mM) and its high molecular mass (44 kDa). Sequential and side chain assignment of IFNAR2-EC and IFNalpha2 in their binary complex helped assign the intermolecular NOEs to the corresponding protons. A docking model of the IFNAR2-EC-IFNalpha2 complex was calculated on the basis of the intermolecular interactions found in this study as well as four double mutant cycle constraints, previously observed NOEs between a single pair of residues and the NMR mapping of the binding sites on IFNAR2-EC and IFNalpha2. Our docking model doubles the buried surface area of the previous model and significantly increases the number of intermolecular hydrogen bonds, salt bridges, and van der Waals interactions. Furthermore, our model reveals the participation of several new regions in the binding site such as the N-terminus and A helix of IFNalpha2 and the C domain of IFNAR2-EC. As a result of these additions, the orientation of IFNAR2-EC relative to IFNalpha2 has changed by 30 degrees in comparison with a previously calculated model that was based on NMR mapping of the binding sites and double mutant cycle constraints. In addition, the new model strongly supports the recently proposed allosteric changes in IFNalpha2 upon binding of IFNAR1-EC to the binary IFNalpha2-IFNAR2-EC complex.

Intermolecular interactions in a 44 kDa interferon-receptor complex detected by asymmetric reverse-protonation and two-dimensional NOESY.,Nudelman I, Akabayov SR, Schnur E, Biron Z, Levy R, Xu Y, Yang D, Anglister J Biochemistry. 2010 Jun 29;49(25):5117-33. PMID:20496919<ref>PMID:20496919</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Interferon 3D structures|Interferon 3D structures]]
*[[Interferon receptor 3D structures|Interferon receptor 3D structures]]
*[[Multiple sclerosis|Multiple sclerosis]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Interferons]]
[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: Akabayov, S R]]
[[Category: Anglister, J]]
[[Category: Biron, Z]]
[[Category: Levy, R]]
[[Category: Nudelman, I]]
[[Category: Schnur, E]]
[[Category: Xu, Y]]
[[Category: Yang, D]]
[[Category: Antiviral defense]]
[[Category: Antiviral protein]]
[[Category: Complex]]
[[Category: Cytokine]]
[[Category: Disulfide bond]]
[[Category: Docking]]
[[Category: Glycoprotein]]
[[Category: Interferon]]
[[Category: Receptor]]
[[Category: Secreted]]