2kz1

From Proteopedia

(Difference between revisions)

Revision as of 17:24, 10 September 2015

Inter-molecular interactions in a 44 kDa interferon-receptor complex detected by asymmetric back-protonation and 2D NOESY

Structural highlights

2kz1 is a 2 chain structure with sequence from Human. This structure supersedes the now removed PDB entry 2ksx. The August 2010 RCSB PDB Molecule of the Month feature on Interferons by David Goodsell is 10.2210/rcsb_pdb/mom_2010_8. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	IFNA2 (HUMAN), IFNABR (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[IFNA2_HUMAN] Produced by macrophages, IFN-alpha have antiviral activities. [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.^[1] ^[2] ^[3] ^[4] ^[5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Novick D, Cohen B, Rubinstein M. The human interferon alpha/beta receptor: characterization and molecular cloning. Cell. 1994 May 6;77(3):391-400. PMID:8181059
↑ Domanski P, Witte M, Kellum M, Rubinstein M, Hackett R, Pitha P, Colamonici OR. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J Biol Chem. 1995 Sep 15;270(37):21606-11. PMID:7665574
↑ Novick D, Cohen B, Tal N, Rubinstein M. Soluble and membrane-anchored forms of the human IFN-alpha/beta receptor. J Leukoc Biol. 1995 May;57(5):712-8. PMID:7759950
↑ Wagner TC, Velichko S, Vogel D, Rani MR, Leung S, Ransohoff RM, Stark GR, Perez HD, Croze E. Interferon signaling is dependent on specific tyrosines located within the intracellular domain of IFNAR2c. Expression of IFNAR2c tyrosine mutants in U5A cells. J Biol Chem. 2002 Jan 11;277(2):1493-9. Epub 2001 Oct 26. PMID:11682488 doi:10.1074/jbc.M108928200
↑ Velichko S, Wagner TC, Turkson J, Jove R, Croze E. STAT3 activation by type I interferons is dependent on specific tyrosines located in the cytoplasmic domain of interferon receptor chain 2c. Activation of multiple STATS proceeds through the redundant usage of two tyrosine residues. J Biol Chem. 2002 Sep 20;277(38):35635-41. Epub 2002 Jun 24. PMID:12105218 doi:10.1074/jbc.M204578200
↑ Nudelman I, Akabayov SR, Schnur E, Biron Z, Levy R, Xu Y, Yang D, Anglister J. Intermolecular interactions in a 44 kDa interferon-receptor complex detected by asymmetric reverse-protonation and two-dimensional NOESY. Biochemistry. 2010 Jun 29;49(25):5117-33. PMID:20496919 doi:10.1021/bi100041f

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2kz1"

@@ Line 2: / Line 2: @@
 <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 [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [http://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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KZ1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2kz1]] is a 2 chain structure with sequence from [http://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 [http://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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KZ1 FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IFNA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IFNABR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IFNA2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IFNABR ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kz1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2kz1 RCSB], [http://www.ebi.ac.uk/pdbsum/2kz1 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2kz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kz1 OCA], [http://pdbe.org/2kz1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kz1 RCSB], [http://www.ebi.ac.uk/pdbsum/2kz1 PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/IFNA2_HUMAN IFNA2_HUMAN]] Produced by macrophages, IFN-alpha have antiviral activities.
+[[http://www.uniprot.org/uniprot/IFNA2_HUMAN IFNA2_HUMAN]] Produced by macrophages, IFN-alpha have antiviral activities. [[http://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]]
@@ Line 26: / Line 26: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2kz1" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 35: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Interferons]]
 [[Category: RCSB PDB Molecule of the Month]]

2kz1

From Proteopedia

Revision as of 17:24, 10 September 2015

Inter-molecular interactions in a 44 kDa interferon-receptor complex detected by asymmetric back-protonation and 2D NOESY

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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