title: Structures of the Sgt2/SGTA dimerization domain with the Get5/UBL4A UBL domain reveal an interaction that forms a conserved dynamic interface.
abstract: In the cytoplasm, the correct delivery of membrane proteins is an essential and highly regulated process. The posttranslational targeting of the important tail-anchor membrane (TA) proteins has recently been under intense investigation. A specialized pathway, called the guided entry of TA proteins (GET) pathway in yeast and the transmembrane domain recognition complex (TRC) pathway in vertebrates, recognizes endoplasmic-reticulum-targeted TA proteins and delivers them through a complex series of handoffs. An early step is the formation of a complex between Sgt2/SGTA, a cochaperone with a presumed ubiquitin-like-binding domain (UBD), and Get5/UBL4A, a ubiquitin-like domain (UBL)-containing protein. We structurally characterize this UBD/UBL interaction for both yeast and human proteins. This characterization is supported by biophysical studies that demonstrate that complex formation is mediated by electrostatics, generating an interface that has high-affinity with rapid kinetics. In total, this work provides a refined model of the interplay of Sgt2 homologs in TA targeting.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Justin W
authors.initials: JW
authors.lastname: Chartron
authors.forename: David G
authors.initials: DG
authors.lastname: VanderVelde
authors.forename: William M
authors.initials: WM
authors.lastname: Clemons
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C510068:Mdy2 protein, S cerevisiae; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C114575:SGTA protein, human; D029701:Saccharomyces cerevisiae Proteins; C520576:Sgt2 protein, S cerevisiae; D025801:Ubiquitin