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

基本情報

• 登録情報: データベース: SASBDB / ID: SASDHE2

試料

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

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

機能・相同性

分子機能:

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

ドメイン・相同性:

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

構成要素:

Insulin-like growth factor 1 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 #3922: ; 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: 0.7396 / P-value: 0.095263; 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: Type 1 insulin-like growth factor receptor ectodomains (IGF-1RΔβ); 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 #1965

名称: IGF1R / タイプ: protein / 記述: Insulin-like growth factor 1 receptor / 分子量: 101.032 / 分子数: 2 / 由来: Homo sapiens / 参照: UniProt: P08069
配列:

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

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: 1.124 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: Type 1 insulin-like growth factor receptor ectodomains (IGF-1RΔβ)
測定日: 2008年4月22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	160

結果

カーブのタイプ: single_conc
コメント: Additional modelling information, including summaries for the related entry SASDHF2 (Insulin receptor ectodomains, IRΔβ), are provided in the full entry zip-archive.

	実験値	Standard	Standard error	Porod
分子量	230 kDa	230 kDa	10	290 kDa
体積	-	-	-	357 nm3

	P(R)	P(R) error	Guinier	Guinier error
前方散乱 I0	0.3467	0.003	0.341	0.005
慣性半径, Rg	5.25 nm	0.03	5.08 nm	0.11

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