SASDAL4: CRM1 RanGTP Snu1 (Exportin-1 + GTP-binding nuclear protein Ran + ...

Basic information

• Entry: Database: SASBDB / ID: SASDAL4

Sample

CRM1 RanGTP Snu1

• Exportin-1Karyopherin (protein), Mus musculus
• GTP-binding nuclear protein Ran (protein), Homo sapiens
• Snurportin-1SPN1 (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 / Heme signaling / HuR (ELAVL1) binds and stabilizes mRNA / RNA import into nucleus / 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 / RNA cap binding / 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 / NLS-dependent protein nuclear import complex / 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 / nucleocytoplasmic transport / nuclear import signal receptor activity / DNA metabolic process / dynein intermediate chain binding / ribosomal subunit export from nucleus / regulation of protein catabolic process / spermatid development / mitotic sister chromatid segregation / ribosomal small subunit export from nucleus / protein localization to nucleus / ribosomal large subunit export from nucleus / sperm flagellum / Cajal body / mRNA export from nucleus / nuclear pore / centriole / protein export from nucleus / viral process / mitotic spindle organization / G protein activity / male germ cell nucleus / hippocampus development / Transcriptional regulation by small RNAs / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / kinetochore / recycling endosome / small GTPase binding / positive regulation of protein import into nucleus / protein import into nucleus / GDP binding / melanosome / ribosome biogenesis / mitotic cell cycle / nuclear envelope / positive regulation of protein binding / snRNP Assembly / midbody / actin cytoskeleton organization / nuclear membrane / DNA-binding transcription factor binding / cadherin binding / ribonucleoprotein complex / protein heterodimerization activity / cell division / protein domain specific binding / intracellular membrane-bounded organelle / GTPase activity / chromatin binding / chromatin / GTP binding / nucleolus / magnesium ion binding / negative regulation of transcription by RNA polymerase II / protein-containing complex / RNA binding / extracellular exosome / nucleoplasm / membrane / nucleus / plasma membrane / cytosol / cytoplasm

Domain/homology:

Snurportin-1 / Snurportin-1, N-terminal / : / Snurportin1 / 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 / Importin-alpha, importin-beta-binding domain / IBB domain profile. / 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:

Snurportin-1 / 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 #70: ; Type: dummy / Software: Dammif / Radius of dummy atoms: 1.90 A; Search similar-shape structures of this assembly by Omokage search (details)
• Model #74: ; Type: dummy / Software: Monsa / Radius of dummy atoms: 1.90 A / Chi-square value: 1.5625; Search similar-shape structures of this assembly by Omokage search (details)
• Model #75: ; Type: dummy / Software: Monsa / Radius of dummy atoms: 1.90 A / Chi-square value: 1.550025; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: CRM1 RanGTP Snu1 / Sample MW: 188.65 kDa / Specimen concentration: 1.00-7.00 / Entity id: 62 / 63 / 64
• Buffer: Name: 50 mM Tris-HCL / pH: 7.5 / Composition: 150 mM NaCl, 1.0 mM DTT

Entity #62

Type: protein / Description: Exportin-1Karyopherin / 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

Entity #64

Type: protein / Description: Snurportin-1SPN1 / Formula weight: 41.14 / Num. of mol.: 1 / Source: Homo sapiens / References: UniProt: O95149
Sequence:

MEELSQALAS SFSVSQDLNS TAAPHPRLSQ YKSKYSSLEQ SERRRRLLEL QKSKRLDYVN HARRLAEDDW TGMESEEENK KDDEEMDIDT VKKLPKHYAN QLMLSEWLID VPSDLGQEWI VVVCPVGKRA LIVASRGSTS AYTKSGYCVN RFSSLLPGGN RRNSTAKDYT ILDCIYNEVN QTYYVLDVMC WRGHPFYDCQ TDFRFYWMHS KLPEEEGLGE KTKLNPFKFV GLKNFPCTPE SLCDVLSMDF PFEVDGLLFY HKQTHYSPGS TPLVGWLRPY MVSDVLGVAV PAGPLTTKPD YAGHQLQQIM EHKKSQKEGM KEKLTHKASE NGHYELEHLS TPKLKGSSHS PDHPGCLMEN

Experimental information

• Beam: Instrument name: DORIS III X33 / City: Hamburg / 国: Germany / Type of source: X-ray synchrotronSynchrotron
• Detector: Name: MAR 345 Image Plate

Scan

Title: CRM1 + RanGTP + SPN1 / Measurement date: Feb 3, 2009 / Cell temperature: 10 °C / Exposure time: 120 sec. / Number of frames: 1 / Unit: 1/nm /

	Min	Max
Q	0.1168	4.943

Result

Type of curve: single_conc /

	Experimental	Porod
MW	190 kDa	190 kDa

	Guinier	P(R)
Forward scattering, I0	1.771	-
Radius of gyration, Rg	4.141 nm	4.1 nm

	Min	Max
D	-	14
Guinier point	29	87