+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDCD2 |
---|---|
Sample | Rab family protein CtRoc-COR GppNHp
|
Function / homology | Function and homology information |
Biological species | Chlorobium tepidum (strain ATCC 49652 / DSM 12025 / NBRC 103806 / TLS) (bacteria) |
Citation | Journal: Nat Commun / Year: 2017 Title: A homologue of the Parkinson's disease-associated protein LRRK2 undergoes a monomer-dimer transition during GTP turnover. Authors: Egon Deyaert / Lina Wauters / Giambattista Guaitoli / Albert Konijnenberg / Margaux Leemans / Susanne Terheyden / Arsen Petrovic / Rodrigo Gallardo / Laura M Nederveen-Schippers / Panagiotis ...Authors: Egon Deyaert / Lina Wauters / Giambattista Guaitoli / Albert Konijnenberg / Margaux Leemans / Susanne Terheyden / Arsen Petrovic / Rodrigo Gallardo / Laura M Nederveen-Schippers / Panagiotis S Athanasopoulos / Henderikus Pots / Peter J M Van Haastert / Frank Sobott / Christian Johannes Gloeckner / Rouslan Efremov / Arjan Kortholt / Wim Versées / Abstract: Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 ...Mutations in LRRK2 are a common cause of genetic Parkinson's disease (PD). LRRK2 is a multi-domain Roco protein, harbouring kinase and GTPase activity. In analogy with a bacterial homologue, LRRK2 was proposed to act as a GTPase activated by dimerization (GAD), while recent reports suggest LRRK2 to exist under a monomeric and dimeric form in vivo. It is however unknown how LRRK2 oligomerization is regulated. Here, we show that oligomerization of a homologous bacterial Roco protein depends on the nucleotide load. The protein is mainly dimeric in the nucleotide-free and GDP-bound states, while it forms monomers upon GTP binding, leading to a monomer-dimer cycle during GTP hydrolysis. An analogue of a PD-associated mutation stabilizes the dimer and decreases the GTPase activity. This work thus provides insights into the conformational cycle of Roco proteins and suggests a link between oligomerization and disease-associated mutations in LRRK2. |
Contact author |
|
-Structure visualization
-Downloads & links
-Data source
SASBDB page | SASDCD2 |
---|
-Related structure data
Related structure data | C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-External links
Related items in Molecule of the Month |
---|
-Models
-Sample
Sample | Name: Rab family protein CtRoc-COR GppNHp / Specimen concentration: 1.00-2.00 |
---|---|
Buffer | Name: 20 mM HEPES 150 mM NaCl 5 mM MgCl2 5% Glycerol 1 mM DTT 200µM GppNHp pH: 7.5 |
Entity #605 | Type: protein / Description: Rab family protein / Formula weight: 64.865 / Num. of mol.: 2 Source: Chlorobium tepidum (strain ATCC 49652 / DSM 12025 / NBRC 103806 / TLS) References: UniProt: Q8KC98_CHL Sequence: MSYYHHHHHH DYDIPTTENL YFQGAMGSDN PLESPPPEIV KQGKEAVRQY FQSIEEARSK GEALVHLQEI KVHLIGDGMA GKTSLLKQLI GETFDPKESQ THGLNVVTKQ APNIKGLEND DELKECLFHF WDFGGQEIMH ASHQFFMTRS SVYMLLLDSR TDSNKHYWLR ...Sequence: MSYYHHHHHH DYDIPTTENL YFQGAMGSDN PLESPPPEIV KQGKEAVRQY FQSIEEARSK GEALVHLQEI KVHLIGDGMA GKTSLLKQLI GETFDPKESQ THGLNVVTKQ APNIKGLEND DELKECLFHF WDFGGQEIMH ASHQFFMTRS SVYMLLLDSR TDSNKHYWLR HIEKYGGKSP VIVVMNKIDE NPSYNIEQKK INERFPAIEN RFHRISCKNG DGVESIAKSL KSAVLHPDSI YGTPLAPSWI KVKEKLVEAT TAQRYLNRTE VEKICNDSGI TDPGERKTLL GYLNNLGIVL YFEALDLSEI YVLDPHWVTI GVYRIINSSK TKNGHLNTSA LGYILNEEQI RCDEYDPAKN NKFTYTLLEQ RYLLDIMKQF ELCYDEGKGL FIIPSNLPTQ IDNEPEITEG EPLRFIMKYD YLPSTIIPRL MIAMQHQILD RMQWRYGMVL KSQDHEGALA KVVAETKDST ITIAIQGEPR CKREYLSIIW YEIKKINANF TNLDVKEFIP LPGHPDELVE YKELLGLEKM GRDEYVSGKL EKVFSVSKML DSVISKEERN KER |
-Experimental information
Beam | Instrument name: SOLEIL SWING / City: Saint-Aubin / 国: France / Type of source: X-ray synchrotron / Wavelength: 0.103 Å / Dist. spec. to detc.: 25 mm | |||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Detector | Name: AVIEX / Type: CCD | |||||||||||||||||||||||||||||||||
Scan | Title: Rab family protein CtRoc-COR GppNHp / Measurement date: Feb 1, 2017 / Exposure time: 0.75 sec. / Number of frames: 31 / Unit: 1/A /
| |||||||||||||||||||||||||||||||||
Distance distribution function P(R) | Sofotware P(R): GNOM 4.6 / Number of points: 475 /
| |||||||||||||||||||||||||||||||||
Result | Type of curve: other /
|