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

Basic information

• Entry: Database: SASBDB / ID: SASDAK4

Sample

CRM1 RanGTP

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

Function / homology

Function:

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

Domain/homology:

Exportin-1, repeat 3 / Chromosome region maintenance repeat / Exportin-1, repeat 2 / Chromosome region maintenance or exportin repeat / CRM1 / Exportin repeat 2 / CRM1 / Exportin repeat 3 / CRM1 C terminal / Exportin-1, C-terminal / CRM1 C terminal / Exportin-1/5 / Exportin-1/Importin-beta-like / Exportin 1-like protein / Ran GTPase / Small GTPase Ran-type domain profile. / Importin-beta N-terminal domain / Importin-beta N-terminal domain / Importin-beta N-terminal domain profile. / 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

Component:

GTP-binding nuclear protein Ran / Exportin-1

• Biological species: Mus musculus (house mouse); Homo sapiens (human)
• Citation: Journal: Structure / Year: 2013; Title: Structural determinants and mechanism of mammalian CRM1 allostery.; Authors: 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 / ; Abstract: 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.

Contact author

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

Models

• Model #69: ; Type: dummy / Software: Dammif / Radius of dummy atoms: 1.90 A; Search similar-shape structures of this assembly by Omokage search (details)
• Model #72: ; Type: dummy / Software: Monsa / Radius of dummy atoms: 1.90 A / Chi-square value: 1.515361; Search similar-shape structures of this assembly by Omokage search (details)
• Model #73: ; Type: dummy / Software: Monsa / Radius of dummy atoms: 1.90 A / Chi-square value: 1.560001; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: CRM1 RanGTP / Sample MW: 147.51 kDa / Specimen concentration: 1.00-10.00 / Entity id: 62 / 63
• Buffer: Name: 50 mM Tris-HCL / pH: 7.5 / Composition: 150 mM NaCl, 1.0 mM DTT

Entity #62

Type: protein / Description: Exportin-1 / Formula weight: 123.09 / Num. of mol.: 1 / Source: Mus musculus / References: UniProt: Q6P5F9
Sequence:

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

Entity #63

Type: protein / Description: GTP-binding nuclear protein Ran / Formula weight: 24.42 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: P62826
Sequence:

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

Experimental information

• Beam: Instrument name: DORIS III X33 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotron
• Detector: Name: Pilatus 2M

Scan

Title: CRM1 + RanGTP (+NES) / Measurement date: Feb 3, 2009 / Cell temperature: 10 °C / Exposure time: 120 sec. / Number of frames: 1 / Unit: 1/nm /

	Min	Max
Q	0.1628	4.837

Result

Type of curve: single_conc /

	Experimental	Porod
MW	140 kDa	140 kDa

	Guinier	P(R)
Forward scattering, I0	1.658	-
Radius of gyration, Rg	3.61 nm	3.6 nm

	Min	Max
D	-	10
Guinier point	26	87