SASDHE2: Type 1 insulin-like growth factor receptor ectodomains (IGF-1RΔβ)

Basic information

• Entry: Database: SASBDB / ID: SASDHE2

Sample

Type 1 insulin-like growth factor receptor ectodomains (IGF-1RΔβ)

• Insulin-like growth factor 1 receptor (protein), IGF1R, Homo sapiens

Function / homology

Function:

cardiac atrium development / negative regulation of cholangiocyte apoptotic process / protein kinase complex / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / insulin-like growth factor binding / IRS-related events triggered by IGF1R / protein transporter activity / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / cellular response to aldosterone / cellular response to zinc ion starvation / insulin receptor complex / insulin-like growth factor I binding / cellular response to testosterone stimulus / insulin receptor activity / transcytosis / negative regulation of hepatocyte apoptotic process / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / cellular response to angiotensin / positive regulation of protein-containing complex disassembly / dendritic spine maintenance / insulin binding / response to L-glutamate / cellular response to insulin-like growth factor stimulus / establishment of cell polarity / positive regulation of cytokinesis / positive regulation of axon regeneration / positive regulation of osteoblast proliferation / amyloid-beta clearance / Respiratory syncytial virus (RSV) attachment and entry / regulation of JNK cascade / insulin receptor substrate binding / G-protein alpha-subunit binding / response to vitamin E / estrous cycle / negative regulation of MAPK cascade / SHC-related events triggered by IGF1R / phosphatidylinositol 3-kinase binding / peptidyl-tyrosine autophosphorylation / cellular response to transforming growth factor beta stimulus / T-tubule / phosphatidylinositol 3-kinase/protein kinase B signal transduction / axonogenesis / cellular response to dexamethasone stimulus / cerebellum development / insulin-like growth factor receptor signaling pathway / hippocampus development / cellular response to estradiol stimulus / response to nicotine / cellular response to glucose stimulus / positive regulation of smooth muscle cell proliferation / insulin receptor binding / receptor protein-tyrosine kinase / caveola / cellular response to mechanical stimulus / cellular response to amyloid-beta / cellular senescence / insulin receptor signaling pathway / positive regulation of cold-induced thermogenesis / protein tyrosine kinase activity / response to ethanol / protein autophosphorylation / positive regulation of MAPK cascade / Extra-nuclear estrogen signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / positive regulation of cell migration / immune response / axon / intracellular membrane-bounded organelle / neuronal cell body / positive regulation of cell population proliferation / protein-containing complex binding / negative regulation of apoptotic process / signal transduction / ATP binding / identical protein binding / membrane / plasma membrane

Domain/homology:

Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / : / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily

Component:

Insulin-like growth factor 1 receptor

• Biological species: Homo sapiens (human)
• Citation: Journal: J Mol Biol / Year: 2009; Title: Solution structure of ectodomains of the insulin receptor family: the ectodomain of the type 1 insulin-like growth factor receptor displays asymmetry of ligand binding accompanied by limited conformational change.; Authors: Andrew E Whitten / Brian J Smith / John G Menting / Mai B Margetts / Neil M McKern / George O Lovrecz / Timothy E Adams / Kim Richards / John D Bentley / Jill Trewhella / Colin W Ward / Michael C Lawrence / ; Abstract: The insulin receptor (IR) and the homologous Type 1 insulin-like growth factor receptor (IGF-1R) are cell-surface tyrosine kinase receptors that effect signaling within the respective pathways of glucose metabolism and normal human growth. While ligand binding to these receptors is assumed to result in a structural transition within the receptor ectodomain that then effects signal transduction across the cell membrane, little is known about the molecular detail of these events. Presented here are small-angle X-ray scattering data obtained from the IR and IGF-1R ectodomains in solution. We show that, in solution, the ectodomains of IR and IGF-1R have a domain disposition that is very similar to that seen in the crystal structure of the ectodomain of IR, despite the constituent domains being in relatively sparse contact and potentially mobile. We also show that the IGF-1R ectodomain is capable of binding up to three molecules of IGF-1 in solution, with surprisingly little apparent change in relative domain disposition compared to the apo form. While the observed 3:1 ligand-binding stoichiometry appears to contradict earlier explanations of the absence of a bell-shaped dose-response curve for IGF-1R in ligand displacement assays, it is readily understood in the context of the harmonic oscillator model of the negative cooperativity of ligand binding to IGF-1R. Taken together, our findings suggest that the structural movements within these receptors upon ligand binding are small and are possibly limited to local rotation of domains.

Contact author

• Andrew Whitten (ANSTO, Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW 2232, Australia)

Models

• Model #3922: ; Type: atomic / Software: (8) / Radius of dummy atoms: 1.90 A / Symmetry: C2 / Chi-square value: 0.7396 / P-value: 0.095263; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Type 1 insulin-like growth factor receptor ectodomains (IGF-1RΔβ); Specimen concentration: 2 mg/ml
• Buffer: Name: 30 mM Tris, 140 mM NaCl, 0.02% w/v sodium azide, / pH: 7.5

Entity #1965

Name: IGF1R / Type: protein / Description: Insulin-like growth factor 1 receptor / Formula weight: 101.032 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P08069
Sequence:

EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVIF EMTNLKDIGL YNLRNITRGA IRIEKNADLC YLSTVDWSLI LDAVSNNYIV GNKPPKECGD LCPGTMEEKP MCEKTTINNE YNYRCWTTNR CQKMCPSTCG KRACTENNEC CHPECLGSCS APDNDTACVA CRHYYYAGVC VPACPPNTYR FEGWRCVDRD FCANILSAES SDSEGFVIHD GECMQECPSG FIRNGSQSMY CIPCEGPCPK VCEEEKKTKT IDSVTSAQML QGCTIFKGNL LINIRRGNNI ASELENFMGL IEVVTGYVKI RHSHALVSLS FLKNLRLILG EEQLEGNYSF YVLDNQNLQQ LWDWDHRNLT IKAGKMYFAF NPKLCVSEIY RMEEVTGTKG RQSKGDINTR NNGERASCES DVLHFTSTTT SKNRIIITWH RYRPPDYRDL ISFTVYYKEA PFKNVTEYDG QDACGSNSWN MVDVDLPPNK DVEPGILLHG LKPWTQYAVY VKAVTLTMVE NDHIRGAKSE ILYIRTNASV PSIPLDVLSA SNSSSQLIVK WNPPSLPNGN LSYYIVRWQR QPQDGYLYRH NYCSKDKIPI RKYADGTIDI EEVTENPKTE VCGGEKGPCC ACPKTEAEKQ AEKEEAEYRK VFENFLHNSI FVPRPERKRR DVMQVANTTM SETEYPFFES RVDNKERTVI SNLRPFTLYR IDIHSCNHEA EKLGCSASNF VFARTMPAEG ADDIPGPVTW EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN YTARIQATSL SGNGSWTDPV FFYVQAKTGY ENFIH

Experimental information

• Beam: Instrument name: Australian Nuclear Science and Technology Organisation Bruker Nanostar; City: Lucas Heights / 国: Australia / Type of source: X-ray in house / Wavelength: 0.15406 Å / Dist. spec. to detc.: 1.124 mm
• Detector: Name: VÅNTEC 2000 / Type: Xe-based gaseous avalanche detector / Pixsize x: 68 mm

Scan

Title: Type 1 insulin-like growth factor receptor ectodomains (IGF-1RΔβ)
Measurement date: Apr 22, 2008 / Storage temperature: 4 °C / Cell temperature: 4 °C / Exposure time: 1800 sec. / Number of frames: 2 / Unit: 1/A /

	Min	Max
Q	0.0096	0.2493

Distance distribution function P(R)

Sofotware P(R): GNOM 4.5a / Number of points: 180 /

	Min	Max
Q	0.009609	0.212
P(R) point	1	180
R	0	160

Result

Type of curve: single_conc
Comments: Additional modelling information, including summaries for the related entry SASDHF2 (Insulin receptor ectodomains, IRΔβ), are provided in the full entry zip-archive.

	Experimental	Standard	Standard error	Porod
MW	230 kDa	230 kDa	10	290 kDa
Volume	-	-	-	357 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	0.3467	0.003	0.341	0.005
Radius of gyration, Rg	5.25 nm	0.03	5.08 nm	0.11

	Min	Max	Error
D	-	16	1
Guinier point	1	15	-