Parkinson disease-associated mutation R1441H in LRRK2 prolongs the "active state" of its GTPase domain

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 11, 2014, Pages 4055-4060

  Liao, Jingling ^a   Wu, Chun Xiang ^a   Burlak, Christopher ^a   Zhang, Sheng ^a   Sahm, Heather ^a   Wang, Mu ^a   Zhang, Zhong Yin ^a   Vogel, Kurt W ^b   Federici, Mark ^b   Riddle, Steve M ^b   Nichols, R Jeremy ^c   Liu, Dali ^d   Cookson, Mark R ^e   Stone, Todd A ^f   Hoang, Quyen Q ^a  

^a INDIANA UNIVERSITY   (United States)

^b Thermo Fisher Scientific   (United States)

^c PARKINSON S INSTITUTE   (United States)

^d LOYOLA UNIVERSITY CHICAGO   (United States)

^e NATIONAL INSTITUTES OF HEALTH   (United States)

^f INDIANA UNIVERSITY   (United States)

Author keywords

Dimer; Monomer; Neurodegenerative disease; Oligomeric states

Indexed keywords

GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATE; LEUCINE RICH REPEAT KINASE 2; MONOMER;

AMINO TERMINAL SEQUENCE; ARTICLE; BINDING AFFINITY; BINDING ASSAY; CONFORMATIONAL TRANSITION; DIMERIZATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME CONFORMATION; ESCHERICHIA COLI; FLUORESCENCE POLARIZATION; GEL PERMEATION CHROMATOGRAPHY; HYDROLYSIS; LIGHT SCATTERING; MICHAELIS CONSTANT; MOLECULAR WEIGHT; NONHUMAN; OLIGOMERIZATION; PARKINSON DISEASE; POINT MUTATION; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PURIFICATION; THERMOSTABILITY;

DIMER; MONOMER; NEURODEGENERATIVE DISEASE; OLIGOMERIC STATES;

BLOTTING, WESTERN; CHROMATOGRAPHY, GEL; CIRCULAR DICHROISM; DIMERIZATION; ELECTROPHORESIS, POLYACRYLAMIDE GEL; GTP PHOSPHOHYDROLASES; HUMANS; MASS SPECTROMETRY; MODELS, MOLECULAR; MUTATION, MISSENSE; PARKINSON DISEASE; PROTEIN CONFORMATION; PROTEIN-SERINE-THREONINE KINASES;

EID: 84896522656     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1323285111     Document Type: Article

References (26)

1. Cookson MR (2010) The role of leucine-rich repeat kinase 2 (LRRK2) in Parkinson's disease. Nat Rev Neurosci 11(12):791-797.
2. Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA (2006) LRRK2 in Parkinson's disease: Protein domains and functional insights. Trends Neurosci 29(5):286-293.
3. Giasson BI, Van Deerlin VM (2008) Mutations in LRRK2 as a cause of Parkinson's disease. Neurosignals 16(1):99-105. (Pubitemid 350308326)
4. Zimprich A, et al. (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44(4):601-607. (Pubitemid 39531225)
5. Paisán-Ruíz C, et al. (2004) Cloning of the gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron 44(4):595-600. (Pubitemid 39531224)
6. Greggio E, et al. (2006) Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis 23(2):329-341. (Pubitemid 44097032)
7. Guo L, et al. (2007) The Parkinson's disease-Associated protein, leucine-rich repeat kinase 2 (LRRK2), is an authentic GTPase that stimulates kinase activity. Exp Cell Res 313(16):3658-3670. (Pubitemid 47404550)
8. Ito G, et al. (2007) GTP binding is essential to the protein kinase activity of LRRK2, a causative gene product for familial Parkinson's disease. Biochemistry 46(5):1380-1388. (Pubitemid 46208485)
9. West AB, et al. (2005) Parkinson's disease-Associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102(46):16842-16847. (Pubitemid 41688864)
10. Deng J, et al. (2008) Structure of the ROC domain from the Parkinson's diseaseassociated leucine-rich repeat kinase 2 reveals a dimeric GTPase. Proc Natl Acad Sci USA 105(5):1499-1504. (Pubitemid 351346543)
11. Gotthardt K, Weyand M, Kortholt A, Van Haastert PJ, Wittinghofer A (2008) Structure of the Roc-COR domain tandem of C. tepidum, a prokaryotic homologue of the human LRRK2 Parkinson kinase. EMBO J 27(16):2239-2249.
12. Wells C, Jiang X, Gutowski S, Sternweis PC (2002) Functional characterization of p115 RhoGEF. Methods Enzymol 345:371-382. (Pubitemid 32954110)
13. Spoerner M, et al. (2010) Conformational states of human rat sarcoma (Ras) protein complexed with its natural ligand GTP and their role for effector interaction and GTP hydrolysis. J Biol Chem 285(51):39768-39778.
14. Cherfils J, Zeghouf M (2011) Chronicles of the GTPase switch. Nat Chem Biol 7(8): 493-495.
15. Cherfils J, Zeghouf M (2013) Regulation of small GTPases by GEFs, GAPs, and GDIs. Physiol Rev 93(1):269-309.
16. McEwen DP, Gee KR, Kang HC, Neubig RR (2002) Fluorescence approaches to study G protein mechanisms. Methods Enzymol 344:403-420.
17. McEwen DP, Gee KR, Kang HC, Neubig RR (2001) Fluorescent BODIPY-GTP analogs: Real-Time measurement of nucleotide binding to G proteins. Anal Biochem 291(1): 109-117. (Pubitemid 32324531)
18. Warnock DE, Schmid SL (1996) Dynamin GTPase, a force-generating molecular switch. Bioessays 18(11):885-893. (Pubitemid 26420245)
19. Traut TW (1994) Physiological concentrations of purines and pyrimidines. Mol Cell Biochem 140(1):1-22. (Pubitemid 24379884)
20. Pingoud A, et al. (1988) Spectroscopic and hydrodynamic studies reveal structural differences in normal and transforming H-ras gene products. Biochemistry 27(13): 4735-4740.
21. Valencia A, Serrano L, Caballero R, Anderson PS, Lacal JC (1988) Conformational alterations detected by circular dichroism induced in the normal ras p21 protein by activating point mutations at position 12, 59, or 61. Eur J Biochem 174(4):621-627.
22. Faelber K, et al. (2011) Crystal structure of nucleotide-free dynamin. Nature 477(7366): 556-560.
23. Ford MGJ, Jenni S, Nunnari J (2011) The crystal structure of dynamin. Nature 477(7366):561-566.
24. Li X, et al. (2007) Leucine-rich repeat kinase 2 (LRRK2)/PARK8 possesses GTPase activity that is altered in familial Parkinson's disease R1441C/G mutants. J Neurochem 103(1): 238-247. (Pubitemid 47404210)
25. Smith WW, et al. (2006) Kinase activity of mutant LRRK2 mediates neuronal toxicity. Nat Neurosci 9(10):1231-1233. (Pubitemid 44454261)
26. Niesen FH, Berglund H, Vedadi M (2007) The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability. Nat Protoc 2(9): 2212-2221. (Pubitemid 351565860)