Genomes and Genes
Ramanujan S Hegde
Affiliation: University of Cambridge
- Voorhees R, Hegde R. Structure of the Sec61 channel opened by a signal sequence. Science. 2016;351:88-91 pubmed publisher..Comparisons with structures of Sec61 in other states suggest a pathway for how hydrophobic signals engage the channel to gain access to the lipid bilayer. ..
- Shao S, Hegde R. Target Selection during Protein Quality Control. Trends Biochem Sci. 2016;41:124-37 pubmed publisher..We discuss principles of high-fidelity target recognition, the decisive event of all protein QC pathways, to guide future work in this area. ..
- Shao S, Murray J, Brown A, Taunton J, Ramakrishnan V, Hegde R. Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes. Cell. 2016;167:1229-1240.e15 pubmed publisher..Our results provide a structural framework for how different states of the mammalian ribosome are selectively recognized by the appropriate decoding factor?GTPase complex to ensure translational fidelity. ..
- Juszkiewicz S, Hegde R. Initiation of Quality Control during Poly(A) Translation Requires Site-Specific Ribosome Ubiquitination. Mol Cell. 2017;65:743-750.e4 pubmed publisher..Thus, ribosome ubiquitination can modulate translation elongation and impacts co-translational quality control to minimize production of aberrant proteins. ..
- Shao S, Rodrigo Brenni M, Kivlen M, Hegde R. Mechanistic basis for a molecular triage reaction. Science. 2017;355:298-302 pubmed publisher..Our results provide a paradigm for how priority and time are encoded within a multichaperone triage system. ..
- Yanagitani K, Juszkiewicz S, Hegde R. UBE2O is a quality control factor for orphans of multiprotein complexes. Science. 2017;357:472-475 pubmed publisher..Thus, UBE2O is a self-contained quality control factor that comprises substrate recognition and ubiquitin transfer activities within a single protein to efficiently target orphans of multiprotein complexes for degradation. ..
- Shao S, Hegde R. Reconstitution of a minimal ribosome-associated ubiquitination pathway with purified factors. Mol Cell. 2014;55:880-890 pubmed publisher..These results reveal the mechanistic logic of the core steps in a ribosome-associated quality control pathway. ..
- Itakura E, Zavodszky E, Shao S, Wohlever M, Keenan R, Hegde R. Ubiquilins Chaperone and Triage Mitochondrial Membrane Proteins for Degradation. Mol Cell. 2016;63:21-33 pubmed publisher..These findings define Ubiquilins as a family of chaperones for cytosolically exposed transmembrane domains and explain how they use ubiquitin to triage clients for degradation via coordinated intra- and intermolecular interactions. ..
- Guna A, Volkmar N, Christianson J, Hegde R. The ER membrane protein complex is a transmembrane domain insertase. Science. 2018;359:470-473 pubmed publisher..Thus, EMC is a transmembrane domain insertase, a function that may explain its widely pleiotropic membrane-associated phenotypes across organisms. ..
- von der Malsburg K, Shao S, Hegde R. The ribosome quality control pathway can access nascent polypeptides stalled at the Sec61 translocon. Mol Biol Cell. 2015;26:2168-80 pubmed publisher..Thus the RQC pathway can target stalled translocation intermediates for degradation from the Sec61 channel. ..