6o60 | pdb_00006o60
Crystal structure of GGTase3-FBXL2-SKP1 complex
Structural highlights
FunctionPublication Abstract from PubMedProtein 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 alpha-subunit, PTAR1, and the catalytic beta-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'. GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase.,Kuchay S, Wang H, Marzio A, Jain K, Homer H, Fehrenbacher N, Philips MR, Zheng N, Pagano M Nat Struct Mol Biol. 2019 Jul;26(7):628-636. doi: 10.1038/s41594-019-0249-3. Epub, 2019 Jun 17. PMID:31209342[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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