SASDAZ7: IL-6R AIR-3A 2:4 complex (AIR-3A + Interleukin-6 receptor subunit...

Basic information

• Entry: Database: SASBDB / ID: SASDAZ7

Sample

IL-6R AIR-3A 2:4 complex

• AIR-3A (RNA)
• Interleukin-6 receptor subunit alpha (protein), IL-6R, Homo sapiens

Function / homology

Function:

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

Domain/homology:

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

Component:

Interleukin-6 receptor subunit alpha

• Biological species: Homo sapiens (human)
• Citation: Journal: 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 / 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 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)

Models

• Model #305: ; Type: dummy / Radius of dummy atoms: 5.50 A / Chi-square value: 1.036; Search similar-shape structures of this assembly by Omokage search (details)
• Model #306: ; Type: mix / Symmetry: P1 / Chi-square value: 1.43; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: IL-6R AIR-3A 2:4 complex / Specimen concentration: 0.2 mg/ml / Entity id: 173 / 174
• Buffer: Name: water / pH: 7.5

Entity #173

Type: RNA / Description: AIR-3A / Formula weight: 6.388 / Num. of mol.: 4
Sequence:

GGGGAGGCUG UGGUGAGGG

Entity #174

Name: 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 QEPCQYSQES QKFSCQLAVP EGDSSFYIVS MCVASSVGSK FSKTQTFQGC GILQPDPPAN ITVTAVARNP RWLSVTWQDP HSWNSSFYRL RFELRYRAER SKTFTTWMVK DLQHHCVIHD AWSGLRHVVQ LRAQEEFGQG EWSEWSPEAM GTPWTESRSP PAENEVSTPM QALTTNKDDD NILFRDSANA TSLPVQ

Experimental information

• Beam: Instrument 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
• Detector: Name: Pilatus 2M

Scan

Title: IL-6R AIR-3A / Measurement date: Oct 1, 2014 / Unit: 1/nm /

	Min	Max
Q	0.0999	4.0114

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 961 /

	Min	Max
Q	0.0132914	0.277168
P(R) point	1	961
R	0	245

Result

Type of curve: single_conc
Comments: The CORAL model fits the experimental curve with a Chi-squared-value of 1.43. The model appears slightly smaller probably because of the presence of free RNA dimers in solution.

	Experimental	Porod
MW	150 kDa	-
Volume	-	150 nm3

	Guinier	P(R)
Forward scattering, I0	3625.94	-
Radius of gyration, Rg	6.7 nm	6.6 nm

	Min	Max
D	-	25
Guinier point	1	25