Home > Publications Database > Structural insights into the GTP-driven monomerization and activation of a bacterial LRRK2 homolog using allosteric nanobodies. > print

001     269345
005     20240809090115.0
024 7 _ |a 10.7554/eLife.94503
|2 doi
024 7 _ |a pmid:38666771
|2 pmid
024 7 _ |a pmc:PMC11052575
|2 pmc
024 7 _ |a altmetric:162911718
|2 altmetric
037 _ _ |a DZNE-2024-00514
041 _ _ |a English
082 _ _ |a 600
100 1 _ |a Galicia, Christian
|0 0000-0001-6080-7533
|b 0
245 _ _ |a Structural insights into the GTP-driven monomerization and activation of a bacterial LRRK2 homolog using allosteric nanobodies.
260 _ _ |a Cambridge
|c 2024
|b eLife Sciences Publications
336 7 _ |a article
|2 DRIVER
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|b journal
|m journal
|0 PUB:(DE-HGF)16
|s 1715673296_2120
|2 PUB:(DE-HGF)
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a Journal Article
|0 0
|2 EndNote
520 _ _ |a Roco proteins entered the limelight after mutations in human LRRK2 were identified as a major cause of familial Parkinson's disease. LRRK2 is a large and complex protein combining a GTPase and protein kinase activity, and disease mutations increase the kinase activity, while presumably decreasing the GTPase activity. Although a cross-communication between both catalytic activities has been suggested, the underlying mechanisms and the regulatory role of the GTPase domain remain unknown. Several structures of LRRK2 have been reported, but structures of Roco proteins in their activated GTP-bound state are lacking. Here, we use single-particle cryo-electron microscopy to solve the structure of a bacterial Roco protein (CtRoco) in its GTP-bound state, aided by two conformation-specific nanobodies: NbRoco1 and NbRoco2. This structure presents CtRoco in an active monomeric state, featuring a very large GTP-induced conformational change using the LRR-Roc linker as a hinge. Furthermore, this structure shows how NbRoco1 and NbRoco2 collaborate to activate CtRoco in an allosteric way. Altogether, our data provide important new insights into the activation mechanism of Roco proteins, with relevance to LRRK2 regulation, and suggest new routes for the allosteric modulation of their GTPase activity.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
|0 G:(DE-HGF)POF4-352
|c POF4-352
|f POF IV
|x 0
588 _ _ |a Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
650 _ 7 |a LRRK2
|2 Other
650 _ 7 |a Parkinson's disease
|2 Other
650 _ 7 |a allosteric mechanism
|2 Other
650 _ 7 |a cryo-EM
|2 Other
650 _ 7 |a molecular biophysics
|2 Other
650 _ 7 |a nanobodies
|2 Other
650 _ 7 |a none
|2 Other
650 _ 7 |a structural biology
|2 Other
650 _ 7 |a Single-Domain Antibodies
|2 NLM Chemicals
650 _ 7 |a Guanosine Triphosphate
|0 86-01-1
|2 NLM Chemicals
650 _ 7 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
|0 EC 2.7.11.1
|2 NLM Chemicals
650 _ 7 |a Bacterial Proteins
|2 NLM Chemicals
650 _ 2 |a Cryoelectron Microscopy
|2 MeSH
650 _ 2 |a Single-Domain Antibodies: metabolism
|2 MeSH
650 _ 2 |a Single-Domain Antibodies: chemistry
|2 MeSH
650 _ 2 |a Guanosine Triphosphate: metabolism
|2 MeSH
650 _ 2 |a Guanosine Triphosphate: chemistry
|2 MeSH
650 _ 2 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: metabolism
|2 MeSH
650 _ 2 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: chemistry
|2 MeSH
650 _ 2 |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2: genetics
|2 MeSH
650 _ 2 |a Bacterial Proteins: metabolism
|2 MeSH
650 _ 2 |a Bacterial Proteins: chemistry
|2 MeSH
650 _ 2 |a Bacterial Proteins: genetics
|2 MeSH
650 _ 2 |a Protein Conformation
|2 MeSH
650 _ 2 |a Allosteric Regulation
|2 MeSH
650 _ 2 |a Models, Molecular
|2 MeSH
650 _ 2 |a Protein Multimerization
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
700 1 _ |a Guaitoli, Giambattista
|0 P:(DE-2719)2811633
|b 1
|u dzne
700 1 _ |a Fislage, Marcus
|0 0000-0002-2527-2657
|b 2
700 1 _ |a Gloeckner, Christian Johannes
|0 P:(DE-2719)2811291
|b 3
700 1 _ |a Versées, Wim
|0 0000-0002-4695-696X
|b 4
773 _ _ |a 10.7554/eLife.94503
|g Vol. 13, p. RP94503
|0 PERI:(DE-600)2687154-3
|p RP94503
|t eLife
|v 13
|y 2024
|x 2050-084X
856 4 _ |u https://pub.dzne.de/record/269345/files/DZNE-2024-00514%20SUP.pdf
856 4 _ |y OpenAccess
|u https://pub.dzne.de/record/269345/files/DZNE-2024-00514.pdf
856 4 _ |x pdfa
|u https://pub.dzne.de/record/269345/files/DZNE-2024-00514%20SUP.pdf?subformat=pdfa
856 4 _ |y OpenAccess
|x pdfa
|u https://pub.dzne.de/record/269345/files/DZNE-2024-00514.pdf?subformat=pdfa
909 C O |o oai:pub.dzne.de:269345
|p openaire
|p open_access
|p VDB
|p driver
|p dnbdelivery
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 1
|6 P:(DE-2719)2811633
910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
|0 I:(DE-588)1065079516
|k DZNE
|b 3
|6 P:(DE-2719)2811291
913 1 _ |a DE-HGF
|b Gesundheit
|l Neurodegenerative Diseases
|1 G:(DE-HGF)POF4-350
|0 G:(DE-HGF)POF4-352
|3 G:(DE-HGF)POF4
|2 G:(DE-HGF)POF4-300
|4 G:(DE-HGF)POF
|v Disease Mechanisms
|x 0
914 1 _ |y 2024
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0200
|2 StatID
|b SCOPUS
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0160
|2 StatID
|b Essential Science Indicators
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1050
|2 StatID
|b BIOSIS Previews
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1190
|2 StatID
|b Biological Abstracts
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0600
|2 StatID
|b Ebsco Academic Search
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)1040
|2 StatID
|b Zoological Record
|d 2023-08-22
915 _ _ |a JCR
|0 StatID:(DE-HGF)0100
|2 StatID
|b ELIFE : 2022
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0501
|2 StatID
|b DOAJ Seal
|d 2022-09-23T12:20:44Z
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0500
|2 StatID
|b DOAJ
|d 2022-09-23T12:20:44Z
915 _ _ |a WoS
|0 StatID:(DE-HGF)0113
|2 StatID
|b Science Citation Index Expanded
|d 2023-08-22
915 _ _ |a Fees
|0 StatID:(DE-HGF)0700
|2 StatID
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0150
|2 StatID
|b Web of Science Core Collection
|d 2023-08-22
915 _ _ |a Creative Commons Attribution CC BY 4.0
|0 LIC:(DE-HGF)CCBY4
|2 HGFVOC
915 _ _ |a OpenAccess
|0 StatID:(DE-HGF)0510
|2 StatID
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b ASC
|d 2023-08-22
915 _ _ |a Article Processing Charges
|0 StatID:(DE-HGF)0561
|2 StatID
|d 2023-08-22
915 _ _ |a IF >= 5
|0 StatID:(DE-HGF)9905
|2 StatID
|b ELIFE : 2022
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0300
|2 StatID
|b Medline
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0320
|2 StatID
|b PubMed Central
|d 2023-08-22
915 _ _ |a DBCoverage
|0 StatID:(DE-HGF)0199
|2 StatID
|b Clarivate Analytics Master Journal List
|d 2023-08-22
915 _ _ |a Peer Review
|0 StatID:(DE-HGF)0030
|2 StatID
|b DOAJ : Anonymous peer review
|d 2022-09-23T12:20:44Z
920 1 _ |0 I:(DE-2719)1210007
|k AG Gloeckner
|l Functional Neuroproteomics and Translational Biomarkers in Neurodegenerative Diseases
|x 0
980 _ _ |a journal
980 _ _ |a VDB
980 _ _ |a UNRESTRICTED
980 _ _ |a I:(DE-2719)1210007
980 1 _ |a FullTexts

LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21