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

基本情報

• 登録情報: データベース: SASBDB / ID: SASDHF2

試料

Insulin receptor ectodomains (IRΔβ)

• Insulin receptor (protein), IR, Homo sapiens

• 機能・相同性: receptor protein-tyrosine kinase / Isoform Long of Insulin receptor
• 生物種: Homo sapiens (ヒト)
• 引用: ジャーナル: J Mol Biol / 年: 2009; タイトル: 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.; 著者: 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 / ; 要旨: 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.

登録者

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

モデル

• モデル #3923: ; タイプ: atomic / ソフトウェア: (8) / ダミー原子の半径: 1.90 A / 対称性: C2 / カイ2乗値: 0.6889 / P-value: 0.024392; Omokage検索でこの集合体の類似形状データを探す (詳細)

試料

• 試料: 名称: Insulin receptor ectodomains (IRΔβ) / 試料濃度: 2 mg/ml
• バッファ: 名称: 30 mM Tris, 140 mM NaCl, 0.02% w/v sodium azide, / pH: 7.5

要素 #1966

名称: IR / タイプ: protein / 記述: Insulin receptor / 分子量: 101.585 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: P06213-1
配列:

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

実験情報

• ビーム: 設備名称: Australian Nuclear Science and Technology Organisation Bruker Nanostar; 地域: Lucas Heights / 国: Australia / 線源: X-ray in house / 波長: 0.15406 Å / スペクトロメータ・検出器間距離: 1.123 mm
• 検出器: 名称: VÅNTEC 2000 / タイプ: Xe-based gaseous avalanche detector / Pixsize x: 68 mm

スキャン

タイトル: Insulin receptor ectodomains (IRΔβ) / 測定日: 2008年12月7日 / 保管温度: 4 °C / セル温度: 4 °C / 照射時間: 1800 sec. / フレーム数: 2 / 単位: 1/A /

	Min	Max
Q	0.0096	0.2493

距離分布関数 P(R)

ソフトウェア P(R): GNOM 4.5a / ポイント数: 180 /

	Min	Max
Q	0.009609	0.212
P(R) point	1	180
R	0	170

結果

カーブのタイプ: single_conc
コメント: 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.

	実験値	Standard	Standard error	Porod
分子量	260 kDa	260 kDa	10	315 kDa
体積	-	-	-	385 nm3

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	0.3942	0.003	0.404	0.006
慣性半径, Rg	5.45 nm	0.03	5.48 nm	0.12

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