2lag

Structure of the 44 kDa complex of interferon-alpha2 with the extracellular part of IFNAR2 obtained by 2D-double difference NOESYStructure of the 44 kDa complex of interferon-alpha2 with the extracellular part of IFNAR2 obtained by 2D-double difference NOESY

Structural highlights

2lag is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 10 models
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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]

Publication Abstract from PubMed

NMR detection of intermolecular interactions between protons in large protein complexes is very challenging since it is difficult to distinguish between weak NOEs from intermolecular interactions and the much larger number of strong intramolecular NOEs. This challenging task is exacerbated by the decrease in signal-to-noise ratio in the often used isotope-edited and isotope-filtered experiments as a result of enhanced T2 relaxation. Here we calculate a double difference spectrum that shows exclusively intermolecular NOEs and manifests the good signal-to-noise ratio in 2D homonuclear NOESY spectra even for large proteins. The method is straightforward and results in a complete picture of all intermolecular interactions involving non exchangeable protons. Ninety seven such 1H-1H NOEs were assigned for the 44 KDa interferon-alpha2/IFNAR2 complex and used for docking these two proteins. The symmetry of the difference spectrum, its superb resolution and unprecedented signal-to-noise ratio in this large protein/receptor complex suggest that this method is generally applicable to study large biopolymeric complexes.

Observation of intermolecular interactions in large protein complexes by 2D-double difference NOESY: application to the 44 kDa interferon-receptor complex.,Nudelman I, Akabayov SR, Scherf T, Anglister J J Am Chem Soc. 2011 Aug 8. PMID:21819146^[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, Scherf T, Anglister J. Observation of intermolecular interactions in large protein complexes by 2D-double difference NOESY: application to the 44 kDa interferon-receptor complex. J Am Chem Soc. 2011 Aug 8. PMID:21819146 doi:10.1021/ja205480v

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OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] 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

[6] Nudelman I, Akabayov SR, Scherf T, Anglister J. Observation of intermolecular interactions in large protein complexes by 2D-double difference NOESY: application to the 44 kDa interferon-receptor complex. J Am Chem Soc. 2011 Aug 8. PMID:21819146 doi:10.1021/ja205480v

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