+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDCA2 |
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Sample | Rab family protein CtRoco GDP
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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 |
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-Structure visualization
-Downloads & links
-Data source
SASBDB page | SASDCA2 |
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-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-External links
Related items in Molecule of the Month |
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-Models
-Sample
Sample | Name: Rab family protein CtRoco GDP / Specimen concentration: 1.00-2.00 |
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Buffer | Name: 20 mM HEPES 150 mM NaCl 5 mM MgCl2 5% Glycerol 1 mM DTT 200µM GDP pH: 7.5 |
Entity #601 | Name: CtRoco / Type: protein / Description: Rab family protein / Formula weight: 127.147 / Num. of mol.: 2 Source: Chlorobium tepidum (strain ATCC 49652 / DSM 12025 / NBRC 103806 / TLS) References: UniProt: Q8KC98 Sequence: MSYYHHHHHH DYDIPTTENL YFQGAMGSMS DLDVIRQIEQ ELGMQLEPVD KLKWYSKGYK LDKDQRVTAI GLYDCGSDTL DRIIQPLESL KSLSELSLSS NQITDISPLA SLNSLSMLWL DRNQITDIAP LASLNSLSML WLFGNKISDI APLESLKSLT ELQLSSNQIT ...Sequence: MSYYHHHHHH DYDIPTTENL YFQGAMGSMS DLDVIRQIEQ ELGMQLEPVD KLKWYSKGYK LDKDQRVTAI GLYDCGSDTL DRIIQPLESL KSLSELSLSS NQITDISPLA SLNSLSMLWL DRNQITDIAP LASLNSLSML WLFGNKISDI APLESLKSLT ELQLSSNQIT DIAPLASLKS LTELSLSGNN ISDIAPLESL KSLTELSLSS NQITDIAPLA SLKSLTELSL SSNQISDIAP LESLKSLTEL QLSRNQISDI APLESLKSLT ELQLSSNQIT DIAPLASLKS LTELQLSRNQ ISDIAPLESL NSLSKLWLNG NQITDIAPLA SLNSLTELEL SSNQITDIAP LASLKSLSTL WLSSNQISDI APLASLESLS ELSLSSNQIS DISPLASLNS LTGFDVRRNP IKRLPETITG FDMEILWNDF SSSGFITFFD NPLESPPPEI VKQGKEAVRQ YFQSIEEARS KGEALVHLQE IKVHLIGDGM AGKTSLLKQL IGETFDPKES QTHGLNVVTK QAPNIKGLEN DDELKECLFH FWDFGGQEIM HASHQFFMTR SSVYMLLLDS RTDSNKHYWL RHIEKYGGKS PVIVVMNKID ENPSYNIEQK KINERFPAIE NRFHRISCKN GDGVESIAKS LKSAVLHPDS IYGTPLAPSW IKVKEKLVEA TTAQRYLNRT EVEKICNDSG ITDPGERKTL LGYLNNLGIV LYFEALDLSE IYVLDPHWVT IGVYRIINSS KTKNGHLNTS ALGYILNEEQ IRCDEYDPAK NNKFTYTLLE QRYLLDIMKQ FELCYDEGKG LFIIPSNLPT QIDNEPEITE GEPLRFIMKY DYLPSTIIPR LMIAMQHQIL DRMQWRYGMV LKSQDHEGAL AKVVAETKDS TITIAIQGEP RCKREYLSII WYEIKKINAN FTNLDVKEFI PLPGHPDELV EYKELLGLEK MGRDEYVSGK LEKVFSVSKM LDSVISKEER NKERLMGDIN IKLENIGNPT IPIHQQVEVN VSQETVQHVE NLQGFFENLK ADILREAELE IDDPKERKRL ANELELAENA ITKMDAAVKS GKNKLKPDVK DRLGEFIDNL ANENSRLRKG IALVMNGAEK VQKLARYYNN VAPFFDLPSV PPVLLGKEKT |
-Experimental information
Beam | Instrument name: SOLEIL SWING / City: Saint-Aubin / 国: France / Type of source: X-ray synchrotron / Wavelength: 0.103 Å | |||||||||||||||||||||||||||||||||
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Detector | Name: AVIEX / Type: CCD | |||||||||||||||||||||||||||||||||
Scan | Title: Rab family protein CtRoco GDP / Measurement date: Jun 17, 2015 / Cell temperature: 25 °C / Exposure time: 0.75 sec. / Number of frames: 36 / Unit: 1/A /
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Distance distribution function P(R) | Sofotware P(R): GNOM 5.0 / Number of points: 203 /
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Result | Type of curve: other /
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