SASDAK4: CRM1 RanGTP (Exportin-1 + GTP-binding nuclear protein Ran)

基本情報

• 登録情報: データベース: SASBDB / ID: SASDAK4

試料

CRM1 RanGTP

• Exportin-1 (protein), Mus musculus
• GTP-binding nuclear protein Ran (protein), Homo sapiens

機能・相同性

分子機能:

Estrogen-dependent nuclear events downstream of ESR-membrane signaling / Cyclin A/B1/B2 associated events during G2/M transition / Heme signaling / HuR (ELAVL1) binds and stabilizes mRNA / Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal / Deactivation of the beta-catenin transactivating complex / Mitotic Prometaphase / EML4 and NUDC in mitotic spindle formation / Resolution of Sister Chromatid Cohesion / annulate lamellae / regulation of proteasomal ubiquitin-dependent protein catabolic process / RHO GTPases Activate Formins / Separation of Sister Chromatids / regulation of centrosome duplication / RNA nuclear export complex / MAPK6/MAPK4 signaling / pre-miRNA export from nucleus / nuclear export signal receptor activity / snRNA import into nucleus / cellular response to mineralocorticoid stimulus / manchette / Regulation of cholesterol biosynthesis by SREBP (SREBF) / importin-alpha family protein binding / regulation of protein export from nucleus / protein localization to nucleolus / Rev-mediated nuclear export of HIV RNA / Nuclear import of Rev protein / GTP metabolic process / NEP/NS2 Interacts with the Cellular Export Machinery / tRNA processing in the nucleus / Postmitotic nuclear pore complex (NPC) reformation / MicroRNA (miRNA) biogenesis / DNA metabolic process / dynein intermediate chain binding / regulation of protein catabolic process / mitotic sister chromatid segregation / protein localization to nucleus / spermatid development / ribosomal large subunit export from nucleus / sperm flagellum / ribosomal small subunit export from nucleus / Cajal body / mRNA export from nucleus / ribosomal subunit export from nucleus / nuclear pore / centriole / viral process / protein export from nucleus / mitotic spindle organization / G protein activity / male germ cell nucleus / hippocampus development / Transcriptional regulation by small RNAs / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / recycling endosome / kinetochore / small GTPase binding / positive regulation of protein import into nucleus / protein import into nucleus / GDP binding / melanosome / positive regulation of protein binding / nuclear envelope / mitotic cell cycle / midbody / actin cytoskeleton organization / nuclear membrane / DNA-binding transcription factor binding / ribonucleoprotein complex / cadherin binding / protein heterodimerization activity / protein domain specific binding / cell division / GTPase activity / chromatin binding / chromatin / nucleolus / GTP binding / negative regulation of transcription by RNA polymerase II / magnesium ion binding / protein-containing complex / RNA binding / extracellular exosome / nucleoplasm / membrane / nucleus / cytoplasm / cytosol

ドメイン・相同性:

Exportin-1, C-terminal / Exportin-1, repeat 3 / Chromosome region maintenance repeat / Exportin-1, repeat 2 / CRM1 C terminal / Chromosome region maintenance or exportin repeat / CRM1 / Exportin repeat 2 / CRM1 / Exportin repeat 3 / CRM1 C terminal / Exportin-1/5 / Exportin-1/Importin-beta-like / Exportin 1-like protein / small GTPase Ran family profile. / Ran GTPase / Importin-beta N-terminal domain profile. / Importin-beta N-terminal domain / Importin-beta N-terminal domain / Importin-beta, N-terminal domain / Ran (Ras-related nuclear proteins) /TC4 subfamily of small GTPases / Rho (Ras homology) subfamily of Ras-like small GTPases / Ras subfamily of RAS small GTPases / Small GTPase / Ras family / Rab subfamily of small GTPases / Armadillo-like helical / Small GTP-binding protein domain / Armadillo-type fold / P-loop containing nucleoside triphosphate hydrolase

構成要素:

GTP-binding nuclear protein Ran / Exportin-1

• 生物種: Mus musculus (ハツカネズミ); Homo sapiens (ヒト)
• 引用: ジャーナル: Structure / 年: 2013; タイトル: Structural determinants and mechanism of mammalian CRM1 allostery.; 著者: Nicole Dölker / Clement E Blanchet / Béla Voß / David Haselbach / Christian Kappel / Thomas Monecke / Dmitri I Svergun / Holger Stark / Ralf Ficner / Ulrich Zachariae / Helmut Grubmüller / Achim Dickmanns / ; 要旨: Proteins carrying nuclear export signals cooperatively assemble with the export factor CRM1 and the effector protein RanGTP. In lower eukaryotes, this cooperativity is coupled to CRM1 conformational changes; however, it is unknown if mammalian CRM1 maintains its compact conformation or shows similar structural flexibility. Here, combinations of small-angle X-ray solution scattering and electron microscopy experiments with molecular dynamics simulations reveal pronounced conformational flexibility in mammalian CRM1 and demonstrate that RanGTP binding induces association of its N- and C-terminal regions to form a toroid structure. The CRM1 toroid is stabilized mainly by local interactions between the terminal regions, rather than by global strain. The CRM1 acidic loop is key in transmitting the effect of this RanGTP-induced global conformational change to the NES-binding cleft by shifting its population to the open state, which displays enhanced cargo affinity. Cooperative CRM1 export complex assembly thus constitutes a highly dynamic process, encompassing an intricate interplay of global and local structural changes.

登録者

• Clement Blanchet (EMBL-Hamburg, European Molecular Biology Laboratory (EMBL) - Hamburg outstation, Notkestraße 85, Geb. 25A, 22607 Hamburg, Deutschland, Germany)

モデル

• モデル #69: ; タイプ: dummy / ソフトウェア: Dammif / ダミー原子の半径: 1.90 A; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #72: ; タイプ: dummy / ソフトウェア: Monsa / ダミー原子の半径: 1.90 A / カイ2乗値: 1.515361; Omokage検索でこの集合体の類似形状データを探す (詳細)
• モデル #73: ; タイプ: dummy / ソフトウェア: Monsa / ダミー原子の半径: 1.90 A / カイ2乗値: 1.560001; 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: CRM1 RanGTP / Sample MW: 147.51 kDa / 試料濃度: 1.00-10.00 / Entity id: 62 / 63
• バッファ: 名称: 50 mM Tris-HCL / pH: 7.5 / 組成: 150 mM NaCl, 1.0 mM DTT

要素 #62

タイプ: protein / 記述: Exportin-1 / 分子量: 123.09 / 分子数: 1 / 由来: Mus musculus / 参照: UniProt: Q6P5F9
配列:

MPAIMTMLAD HAARQLLDFS QKLDINLLDN VVNCLYHGEG AQQRMAQEVL THLKEHPDAW TRVDTILEFS QNMNTKYYGL QILENVIKTR WKILPRNQCE GIKKYVVGLI IKTSSDPTCV EKEKVYIGKL NMILVQILKQ EWPKHWPTFI SDIVGASRTS ESLCQNNMVI LKLLSEEVFD FSSGQITQVK AKHLKDSMCN EFSQIFQLCQ FVMENSQNAP LVHATLETLL RFLNWIPLGY IFETKLISTL IYKFLNVPMF RNVSLKCLTE IAGVSVSQYE EQFETLFTLT MMQLKQMLPL NTNIRLAYSN GKDDEQNFIQ NLSLFLCTFL KEHGQLLEKR LNLREALMEA LHYMLLVSEV EETEIFKICL EYWNHLAAEL YRESPFSTSA SPLLSGSQHF DIPPRRQLYL TVLSKVRLLM VSRMAKPEEV LVVENDQGEV VREFMKDTDS INLYKNMRET LVYLTHLDYV DTEIIMTKKL QNQVNGTEWS WKNLNTLCWA IGSISGAMHE EDEKRFLVTV IKDLLGLCEQ KRGKDNKAII ASNIMYIVGQ YPRFLRAHWK FLKTVVNKLF EFMHETHDGV QDMACDTFIK IAQKCRRHFV QVQVGEVMPF IDEILNNINT IICDLQPQQV HTFYEAVGYM IGAQTDQTVQ EHLIEKYMLL PNQVWDSIIQ QATKNVDILK DPETVKQLGS ILKTNVRACK AVGHPFVIQL GRIYLDMLNV YKCLSENISA AIQANGEMVT KQPLIRSMRT VKRETLKLIS GWVSRSNDPQ MVAENFVPPL LDAVLIDYQR NVPAAREPEV LSTMAIIVNK LGGHITAEIP QIFDAVFECT LNMINKDFEE YPEHRTNFFL LLQAVNSHCF PAFLAIPPAQ FKLVLDSIIW AFKHTMRNVA DTGLQILFTL LQNVAQEEAA AQSFYQTYFC DILQHIFSVV TDTSHTAGLT MHASILAYMF NLVEEGKIST PLNPGNPVNN QMFIQDYVAN LLKSAFPHLQ DAQVKLFVTG LFSLNQDIPA FKEHLRDFLV QIKEFAGEDT SDLFLEERET ALRQAQEEKH KLQMSVPGIL NPHEIPEEMC D

要素 #63

タイプ: protein / 記述: GTP-binding nuclear protein Ran / 分子量: 24.42 / 分子数: 1 / 由来: Homo sapiens / 参照: UniProt: P62826
配列:

MAAQGEPQVQ FKLVLVGDGG TGKTTFVKRH LTGEFEKKYV ATLGVEVHPL VFHTNRGPIK FNVWDTAGQE KFGGLRDGYY IQAQCAIIMF DVTSRVTYKN VPNWHRDLVR VCENIPIVLC GNKVDIKDRK VKAKSIVFHR KKNLQYYDIS AKSNYNFEKP FLWLARKLIG DPNLEFVAMP ALAPPEVVMD PALAAQYEHD LEVAQTTALP DEDDDL

実験情報

• ビーム: 設備名称: DORIS III X33 / 地域: Hamburg / 国: Germany / 線源: X-ray synchrotron
• 検出器: 名称: Pilatus 2M

スキャン

タイトル: CRM1 + RanGTP (+NES) / 測定日: 2009年2月3日 / セル温度: 10 °C / 照射時間: 120 sec. / フレーム数: 1 / 単位: 1/nm /

	Min	Max
Q	0.1628	4.837

結果

カーブのタイプ: single_conc /

	実験値	Porod
分子量	140 kDa	140 kDa

	Guinier	P(R)
前方散乱 I0	1.658	-
慣性半径, Rg	3.61 nm	3.6 nm

	Min	Max
D	-	10
Guinier point	26	87