SASDHF2: Insulin receptor ectodomains (IRΔβ) (Insulin receptor, IR)

Basic information

• Entry: Database: SASBDB / ID: SASDHF2

Sample

Insulin receptor ectodomains (IRΔβ)

• Insulin receptor (protein), IR, Homo sapiens

• Function / homology: receptor protein-tyrosine kinase / Isoform Long of Insulin 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 #3923: ; Type: atomic / Software: (8) / Radius of dummy atoms: 1.90 A / Symmetry: C2 / Chi-square value: 0.6889 / P-value: 0.024392; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Insulin receptor ectodomains (IRΔβ) / Specimen concentration: 2 mg/ml
• Buffer: Name: 30 mM Tris, 140 mM NaCl, 0.02% w/v sodium azide, / pH: 7.5

Entity #1966

Name: IR / Type: protein / Description: Insulin receptor / Formula weight: 101.585 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P06213-1
Sequence:

HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNLT VIRGSRLFFN YALVIFEMVH LKELGLYNLM NITRGSVRIE KNNELCYLAT IDWSRILDSV EDNYIVLNKD DNEECGDICP GTAKGKTNCP ATVINGQFVE RCWTHSHCQK VCPTICKSHG CTAEGLCCHS ECLGNCSQPD DPTKCVACRN FYLDGRCVET CPPPYYHFQD WRCVNFSFCQ DLHHKCKNSR RQGCHQYVIH NNKCIPECPS GYTMNSSNLL CTPCLGPCPK VCHLLEGEKT IDSVTSAQEL RGCTVINGSL IINIRGGNNL AAELEANLGL IEEISGYLKI RRSYALVSLS FFRKLRLIRG ETLEIGNYSF YALDNQNLRQ LWDWSKHNLT TTQGKLFFHY NPKLCLSEIH KMEEVSGTKG RQERNDIALK TNGDKASCEN ELLKFSYIRT SFDKILLRWE PYWPPDFRDL LGFMLFYKEA PYQNVTEFDG QDACGSNSWT VVDIDPPLRS NDPKSQNHPG WLMRGLKPWT QYAIFVKTLV TFSDERRTYG AKSDIIYVQT DATNPSVPLD PISVSNSSSQ IILKWKPPSD PNGNITHYLV FWERQAEDSE LFELDYCLKG LKLPSRTWSP PFESEDSQKH NQSEYEDSAG ECCSCPKTDS QILKELEESS FRKTFEDYLH NVVFVPRPSR KRRSLGDVGN EEHRPFEKVV NKESLVISGL RHFTGYRIEL QACNQDTPEE RCSVAAYVSA RTMPEAKADD IVGPVTHEIF ENNVVHLMWQ EPKEPNGLIV LYEVSYRRYG DEELHLCVSR KHFALERGCR LRGLSPGNYS VRIRATSLAG NGSWTEPTYF YVTDYL

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.: 1.123 mm
• Detector: Name: VÅNTEC 2000 / Type: Xe-based gaseous avalanche detector / Pixsize x: 68 mm

Scan

Title: Insulin receptor ectodomains (IRΔβ) / Measurement date: Dec 7, 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	170

Result

Type of curve: single_conc
Comments: Additional modelling information, including summaries for the related entry SASDHE2 (Type 1 insulin-like growth factor receptor ectodomains, IGF-1RΔβ), are provided in the full entry zip-archive.

	Experimental	Standard	Standard error	Porod
MW	260 kDa	260 kDa	10	315 kDa
Volume	-	-	-	385 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	0.3942	0.003	0.404	0.006
Radius of gyration, Rg	5.45 nm	0.03	5.48 nm	0.12

	Min	Max	Error
D	-	17	1
Guinier point	1	13	-