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- SASDAY7: IL-6R tetramer-dimer equilibrium (Interleukin-6 receptor subunit ... -

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Basic information

Entry
Database: SASBDB / ID: SASDAY7
SampleIL-6R tetramer-dimer equilibrium
  • Interleukin-6 receptor subunit alpha (protein), IL-6R, Homo sapiens
  • Interleukin-6 receptor subunit alpha (protein), IL-6R, Homo sapiens
Function / homology
Function and homology information


ciliary neurotrophic factor binding / interleukin-6 receptor activity / interleukin-6 binding / hepatic immune response / : / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor-mediated signaling pathway / ciliary neurotrophic factor receptor complex / interleukin-6 receptor complex ...ciliary neurotrophic factor binding / interleukin-6 receptor activity / interleukin-6 binding / hepatic immune response / : / interleukin-11 receptor activity / interleukin-11 binding / ciliary neurotrophic factor-mediated signaling pathway / ciliary neurotrophic factor receptor complex / interleukin-6 receptor complex / negative regulation of collagen biosynthetic process / endocrine pancreas development / T-helper 17 cell lineage commitment / negative regulation of interleukin-8 production / positive regulation of glomerular mesangial cell proliferation / vascular endothelial growth factor production / positive regulation of leukocyte chemotaxis / neutrophil mediated immunity / cytokine receptor activity / Interleukin-6 signaling / interleukin-6-mediated signaling pathway / MAPK3 (ERK1) activation / monocyte chemotaxis / MAPK1 (ERK2) activation / positive regulation of osteoblast differentiation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of chemokine production / extrinsic apoptotic signaling pathway / response to cytokine / acute-phase response / positive regulation of smooth muscle cell proliferation / cytokine-mediated signaling pathway / positive regulation of interleukin-6 production / Transcriptional regulation of granulopoiesis / positive regulation of peptidyl-tyrosine phosphorylation / Interleukin-4 and Interleukin-13 signaling / defense response to Gram-negative bacterium / Potential therapeutics for SARS / positive regulation of MAPK cascade / receptor complex / defense response to Gram-positive bacterium / apical plasma membrane / external side of plasma membrane / positive regulation of cell population proliferation / enzyme binding / protein homodimerization activity / extracellular space / extracellular region / plasma membrane
Similarity search - Function
Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / : / Immunoglobulin / Immunoglobulin domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type ...Type I cytokine receptor, cytokine-binding domain / Interleukin-6 receptor alpha chain, binding / Long hematopoietin receptor, soluble alpha chain, conserved site / Long hematopoietin receptor, soluble alpha chains family signature. / : / Immunoglobulin / Immunoglobulin domain / Fibronectin type 3 domain / Immunoglobulin subtype 2 / Immunoglobulin C-2 Type / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Immunoglobulin subtype / Immunoglobulin / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold
Similarity search - Domain/homology
Interleukin-6 receptor subunit alpha
Similarity search - Component
Biological speciesHomo sapiens (human)
CitationJournal: RNA Biol / Year: 2016
Title: Structure and target interaction of a G-quadruplex RNA-aptamer.
Authors: Kristina Szameit / Katharina Berg / Sven Kruspe / Erica Valentini / Eileen Magbanua / Marcel Kwiatkowski / Isaure Chauvot de Beauchêne / Boris Krichel / Kira Schamoni / Charlotte Uetrecht / ...Authors: Kristina Szameit / Katharina Berg / Sven Kruspe / Erica Valentini / Eileen Magbanua / Marcel Kwiatkowski / Isaure Chauvot de Beauchêne / Boris Krichel / Kira Schamoni / Charlotte Uetrecht / Dmitri I Svergun / Hartmut Schlüter / Martin Zacharias / Ulrich Hahn /
Abstract: G-quadruplexes have recently moved into focus of research in nucleic acids, thereby evolving in scientific significance from exceptional secondary structure motifs to complex modulators of gene ...G-quadruplexes have recently moved into focus of research in nucleic acids, thereby evolving in scientific significance from exceptional secondary structure motifs to complex modulators of gene regulation. Aptamers (nucleic acid based ligands with recognition properties for a specific target) that form Gquadruplexes may have particular potential for therapeutic applications as they combine the characteristics of specific targeting and Gquadruplex mediated stability and regulation. We have investigated the structure and target interaction properties of one such aptamer: AIR-3 and its truncated form AIR-3A. These RNA aptamers are specific for human interleukin-6 receptor (hIL-6R), a key player in inflammatory diseases and cancer, and have recently been exploited for in vitro drug delivery studies. With the aim to resolve the RNA structure, global shape, RNA:protein interaction site and binding stoichiometry, we now investigated AIR-3 and AIR-3A by different methods including RNA structure probing, Small Angle X-ray scattering and microscale thermophoresis. Our findings suggest a broader spectrum of folding species than assumed so far and remarkable tolerance toward different modifications. Mass spectrometry based binding site analysis, supported by molecular modeling and docking studies propose a general Gquadruplex affinity for the target molecule hIL-6R.
Contact author
  • Erica Valentini (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Models

Model #300
Type: mix / Software: CORAL / Chi-square value: 2.49
Search similar-shape structures of this assembly by Omokage search (details)
Model #301
Type: mix / Software: CORAL-OLIGOMER / Radius of dummy atoms: 1.90 A / Chi-square value: 1.33
Search similar-shape structures of this assembly by Omokage search (details)
Model #302
Type: mix / Software: CORAL-OLIGOMER / Radius of dummy atoms: 1.90 A / Comment: extended dimer / Chi-square value: 1.33
Search similar-shape structures of this assembly by Omokage search (details)
Model #303
Type: mix / Software: CORAL-OLIGOMER / Radius of dummy atoms: 1.90 A / Chi-square value: 1.92
Search similar-shape structures of this assembly by Omokage search (details)
Model #304
Type: mix / Software: CORAL-OLIGOMER / Comment: compact dimer / Chi-square value: 1.92
Search similar-shape structures of this assembly by Omokage search (details)

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Sample

SampleName: IL-6R tetramer-dimer equilibrium / Specimen concentration: 0.1 mg/ml / Entity id: 171 / 174
BufferName: water / pH: 7.5
Entity #171Name: IL-6R / Type: protein / Description: Interleukin-6 receptor subunit alpha / Formula weight: 40.964 / Num. of mol.: 4 / Source: Homo sapiens / References: UniProt: P08887
Sequence: MRAWIFFLLC LAGRALAAPL VHHHHHHALA PRRCPAQEVA RGVLTSLPGD SVTLTCPGVE PEDNATVHWV LRKPAAGSHP SRWAGMGRRL LLRSVQLHDS GNYSCYRAGR PAGTVHLLVD VPPEEPQLSC FRKSPLSNVV CEWGPRSTPS LTTKAVLLVR KFQNSPAEDF ...Sequence:
MRAWIFFLLC LAGRALAAPL VHHHHHHALA PRRCPAQEVA RGVLTSLPGD SVTLTCPGVE PEDNATVHWV LRKPAAGSHP SRWAGMGRRL LLRSVQLHDS GNYSCYRAGR PAGTVHLLVD VPPEEPQLSC FRKSPLSNVV CEWGPRSTPS LTTKAVLLVR KFQNSPAEDF QEPCQYSQES QKFSCQLAVP EGDSSFYIVS MCVASSVGSK FSKTQTFQGC GILQPDPPAN ITVTAVARNP RWLSVTWQDP HSWNSSFYRL RFELRYRAER SKTFTTWMVK DLQHHCVIHD AWSGLRHVVQ LRAQEEFGQG EWSEWSPEAM GTPWTESRSP PAENEVSTPM QALTTNKDDD NILFRDSANA TSLPVQ
Entity #174Name: IL-6R / Type: protein / Description: Interleukin-6 receptor subunit alpha / Formula weight: 40.964 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P08887
Sequence: MRAWIFFLLC LAGRALAAPL VHHHHHHALA PRRCPAQEVA RGVLTSLPGD SVTLTCPGVE PEDNATVHWV LRKPAAGSHP SRWAGMGRRL LLRSVQLHDS GNYSCYRAGR PAGTVHLLVD VPPEEPQLSC FRKSPLSNVV CEWGPRSTPS LTTKAVLLVR KFQNSPAEDF ...Sequence:
MRAWIFFLLC LAGRALAAPL VHHHHHHALA PRRCPAQEVA RGVLTSLPGD SVTLTCPGVE PEDNATVHWV LRKPAAGSHP SRWAGMGRRL LLRSVQLHDS GNYSCYRAGR PAGTVHLLVD VPPEEPQLSC FRKSPLSNVV CEWGPRSTPS LTTKAVLLVR KFQNSPAEDF QEPCQYSQES QKFSCQLAVP EGDSSFYIVS MCVASSVGSK FSKTQTFQGC GILQPDPPAN ITVTAVARNP RWLSVTWQDP HSWNSSFYRL RFELRYRAER SKTFTTWMVK DLQHHCVIHD AWSGLRHVVQ LRAQEEFGQG EWSEWSPEAM GTPWTESRSP PAENEVSTPM QALTTNKDDD NILFRDSANA TSLPVQ

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Experimental information

BeamInstrument name: Diamond Light Source B21 / City: Oxfordshire / 国: UK / Shape: 1 x 5 mm / Type of source: X-ray synchrotron / Dist. spec. to detc.: 3.9 mm
DetectorName: Pilatus 2M
Scan
Title: IL-6R / Measurement date: Oct 1, 2014 / Unit: 1/nm /
MinMax
Q0.0257 4.0114
Distance distribution function P(R)
Sofotware P(R): GNOM 5.0 / Number of points: 453 /
MinMax
Q0.00696941 0.131211
P(R) point1 453
R0 202.1
Result
Type of curve: single_conc
Comments: The curve was fitted with a tetramer obtained with CORAL from the unit cell tetrameric structure of the pdb code 1N26 with a Chi-squared-value of 2.49. Since the experimental MW appeared ...Comments: The curve was fitted with a tetramer obtained with CORAL from the unit cell tetrameric structure of the pdb code 1N26 with a Chi-squared-value of 2.49. Since the experimental MW appeared smaller than a tetramer (confirmed by a not-fitting tetrameric model) we tried to fit a mixture of tetramer-dimer using OLIGOMER. Two possible dimers were possible: a compact and an extended one. With the compact dimer mixture OLIGOMER estimated a volume fraction of 65% tetramer and 35% dimer and a corresponding Chi-squared-value of 1.92. With the extended dimer mixture OLIGOMER estimated a volume fraction of 47% tetramer and 53% dimer and a improved Chi-squared-value of 1.33.
ExperimentalPorodPorod error
MW143 kDa143 kDa-
Volume-240 nm340

GuinierP(R)
Forward scattering, I00.025 -
Radius of gyration, Rg4.9 nm5.1 nm

MinMaxError
D-20 2
Guinier point17 76 -

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