GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase.
Journal
Nature structural & molecular biology
ISSN: 1545-9985
Titre abrégé: Nat Struct Mol Biol
Pays: United States
ID NLM: 101186374
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
27
01
2019
accepted:
10
05
2019
pubmed:
19
6
2019
medline:
26
2
2020
entrez:
19
6
2019
Statut:
ppublish
Résumé
Protein prenylation is believed to be catalyzed by three heterodimeric enzymes: FTase, GGTase1 and GGTase2. Here we report the identification of a previously unknown human prenyltransferase complex consisting of an orphan prenyltransferase α-subunit, PTAR1, and the catalytic β-subunit of GGTase2, RabGGTB. This enzyme, which we named GGTase3, geranylgeranylates FBXL2 to allow its localization at cell membranes, where this ubiquitin ligase mediates the polyubiquitylation of membrane-anchored proteins. In cells, FBXL2 is specifically recognized by GGTase3 despite having a typical carboxy-terminal CaaX prenylation motif that is predicted to be recognized by GGTase1. Our crystal structure analysis of the full-length GGTase3-FBXL2-SKP1 complex reveals an extensive multivalent interface specifically formed between the leucine-rich repeat domain of FBXL2 and PTAR1, which unmasks the structural basis of the substrate-enzyme specificity. By uncovering a missing prenyltransferase and its unique mode of substrate recognition, our findings call for a revision of the 'prenylation code'.
Identifiants
pubmed: 31209342
doi: 10.1038/s41594-019-0249-3
pii: 10.1038/s41594-019-0249-3
pmc: PMC6609460
mid: NIHMS1529146
doi:
Substances chimiques
F-Box Proteins
0
FBXL2 protein, human
0
Protein Subunits
0
Polyubiquitin
120904-94-1
Alkyl and Aryl Transferases
EC 2.5.-
RABGGTB protein, human
EC 2.5.-
Dimethylallyltranstransferase
EC 2.5.1.1
PTAR1 protein, human
EC 2.5.1.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
628-636Subventions
Organisme : NCI NIH HHS
ID : R01 CA076584
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM057587
Pays : United States
Références
J Neurosci. 2016 Sep 14;36(37):9722-38
pubmed: 27629721
Mol Cell. 2005 May 13;18(4):425-34
pubmed: 15893726
J Neurosci. 2015 Dec 16;35(50):16545-60
pubmed: 26674878
Nat Chem Biol. 2009 Apr;5(4):197-8
pubmed: 19295521
J Biol Chem. 1996 Mar 8;271(10):5289-92
pubmed: 8621375
EMBO J. 2003 Nov 17;22(22):5963-74
pubmed: 14609943
Nat Methods. 2013 Aug;10(8):730-6
pubmed: 23921808
Nature. 2002 Oct 10;419(6907):645-50
pubmed: 12374986
Nature. 2013 Apr 4;496(7443):64-8
pubmed: 23503662
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11626-31
pubmed: 11027361
Nat Rev Mol Cell Biol. 2013 Jun;14(6):369-81
pubmed: 23657496
Nature. 2007 Apr 5;446(7136):640-5
pubmed: 17410169
Annu Rev Biochem. 1996;65:241-69
pubmed: 8811180
BMC Biochem. 2006 Feb 28;7:6
pubmed: 16507103
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
pubmed: 15299374
Nature. 2000 Nov 16;408(6810):381-6
pubmed: 11099048
Nat Rev Mol Cell Biol. 2016 Feb;17(2):110-22
pubmed: 26790532
J Lipid Res. 2006 Apr;47(4):681-99
pubmed: 16477080
Cell. 2007 Sep 7;130(5):943-57
pubmed: 17803915
Nat Rev Cancer. 2011 Oct 24;11(11):775-91
pubmed: 22020205
Chembiochem. 2010 Jun 14;11(9):1194-201
pubmed: 20432425
Science. 2015 Nov 27;350(6264):1092-6
pubmed: 26472760
Methods Enzymol. 1997;276:307-26
pubmed: 27754618
Mol Cell Biol. 2011 May;31(9):1905-20
pubmed: 21343341
Structure. 2000 Feb 15;8(2):209-22
pubmed: 10673434
Cell. 2015 Jul 16;162(2):425-440
pubmed: 26186194
EMBO J. 2008 Sep 17;27(18):2444-56
pubmed: 18756270
Mol Cell. 2013 Oct 10;52(1):9-24
pubmed: 24035498
J Biol Chem. 1995 Mar 17;270(11):6221-6
pubmed: 7890759
J Lipid Res. 2006 May;47(5):883-91
pubmed: 16543601
Nat Rev Mol Cell Biol. 2011 Dec 22;13(1):39-51
pubmed: 22189424
Nature. 2017 Jun 22;546(7659):554-558
pubmed: 28614300
J Neurosci. 2017 Apr 5;37(14):3887-3895
pubmed: 28292828
Clin Cancer Res. 2015 Apr 15;21(8):1819-27
pubmed: 25878363
Nature. 2002 Apr 18;416(6882):703-9
pubmed: 11961546
J Biol Chem. 1997 May 30;272(22):14093-7
pubmed: 9162034
Biochemistry. 1995 May 23;34(20):6857-62
pubmed: 7756316
Nat Cell Biol. 2013 May;15(5):472-80
pubmed: 23604317
Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
pubmed: 12393927
J Biol Chem. 1997 May 30;272(22):14459-64
pubmed: 9162087
Mol Cell. 2003 Feb;11(2):483-94
pubmed: 12620235
Cell Rep. 2018 Oct 23;25(4):833-840.e3
pubmed: 30355490
J Biol Chem. 2015 Jul 17;290(29):18124-18133
pubmed: 26037928
J Struct Biol. 2003 Jan;141(1):93-5
pubmed: 12576024
Oncogene. 1995 May 18;10(10):1905-13
pubmed: 7761092
Genome Biol. 2003;4(4):212
pubmed: 12702202
Science. 1997 Mar 21;275(5307):1800-4
pubmed: 9065406
Nat Rev Drug Discov. 2014 Dec;13(12):889-903
pubmed: 25394868
J Biol Chem. 2001 Dec 28;276(52):48637-43
pubmed: 11675392