title: Molecular architecture of the yeast Elongator complex reveals an unexpected asymmetric subunit arrangement.
abstract: Elongator is a ~850 kDa protein complex involved in multiple processes from transcription to tRNA modification. Conserved from yeast to humans, Elongator is assembled from two copies of six unique subunits (Elp1 to Elp6). Despite the wealth of structural data on the individual subunits, the overall architecture and subunit organization of the full Elongator and the molecular mechanisms of how it exerts its multiple activities remain unclear. Using single-particle electron microscopy (EM), we revealed that yeast Elongator adopts a bilobal architecture and an unexpected asymmetric subunit arrangement resulting from the hexameric Elp456 subassembly anchored to one of the two Elp123 lobes that form the structural scaffold. By integrating the EM data with available subunit crystal structures and restraints generated from cross-linking coupled to mass spectrometry, we constructed a multiscale molecular model that showed the two Elp3, the main catalytic subunit, are located in two distinct environments. This work provides the first structural insights into Elongator and a framework to understand the molecular basis of its multifunctionality.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Dheva T
authors.initials: DT
authors.lastname: Setiaputra
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Derrick Th
authors.initials: DT
authors.lastname: Cheng
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Hansen
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Udit
authors.initials: U
authors.lastname: Dalwadi
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Cindy Hy
authors.initials: CH
authors.lastname: Lam
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: To
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, China.
authors.forename: Meng-Qiu
authors.initials: MQ
authors.lastname: Dong
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, BC, Canada calvin.yip@ubc.ca.
authors.forename: Calvin K
authors.identifier: 0000-0003-1779-9501
authors.initials: CK
authors.lastname: Yip
mesh_terms: D017124:Conserved Sequence; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013058:Mass Spectrometry; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D017384:Sequence Deletion; D013329:Structure-Activity Relationship
chemical_list: D005656:Fungal Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases
keywords: Elongator; electron microscopy; structure; tRNA modification