Ramanujan S Hegde


Affiliation: University of Cambridge
Country: UK


  1. Mateja A, Paduch M, Chang H, Szydlowska A, Kossiakoff A, Hegde R, et al. Protein targeting. Structure of the Get3 targeting factor in complex with its membrane protein cargo. Science. 2015;347:1152-5 pubmed publisher
    ..Our data elucidate the mechanism of TA protein recognition and shielding by Get3 and suggest general principles of hydrophobic domain chaperoning by cellular targeting factors. ..
  2. Chitwood P, Hegde R. The Role of EMC during Membrane Protein Biogenesis. Trends Cell Biol. 2019;29:371-384 pubmed publisher
    ..Given the large proportion of genes encoding membrane proteins, a central role for EMC as a TMD insertion factor can explain its high abundance, wide conservation, and pleiotropic phenotypes. ..
  3. Chitwood P, Juszkiewicz S, Guna A, Shao S, Hegde R. EMC Is Required to Initiate Accurate Membrane Protein Topogenesis. Cell. 2018;175:1507-1519.e16 pubmed publisher
    ..Thus, EMC inserts TMDs co-translationally and cooperates with the Sec61 translocon to ensure accurate topogenesis of many membrane proteins. ..
  4. Juszkiewicz S, Chandrasekaran V, Lin Z, Kraatz S, Ramakrishnan V, Hegde R. ZNF598 Is a Quality Control Sensor of Collided Ribosomes. Mol Cell. 2018;72:469-481.e7 pubmed publisher
    ..These findings illustrate how higher-order ribosome architecture can be exploited by cellular factors to monitor translation status. ..
  5. Juszkiewicz S, Hegde R. Quality Control of Orphaned Proteins. Mol Cell. 2018;71:443-457 pubmed publisher
    ..In this review, we discuss the challenges faced by a cell of minimizing orphaned proteins, the quality control systems that recognize orphans, and the consequences of excess orphans for protein homeostasis and disease. ..
  6. Voorhees R, Fernández I, Scheres S, Hegde R. Structure of the mammalian ribosome-Sec61 complex to 3.4 Å resolution. Cell. 2014;157:1632-43 pubmed publisher
    ..The high-resolution structure of the mammalian ribosome-Sec61 complex provides a valuable reference for future functional and structural studies. ..
  7. Satpute Krishnan P, Ajinkya M, Bhat S, Itakura E, Hegde R, Lippincott Schwartz J. ER stress-induced clearance of misfolded GPI-anchored proteins via the secretory pathway. Cell. 2014;158:522-33 pubmed publisher
    ..Thus, this rapid response alleviates the elevated burden of misfolded proteins in the ER at the onset of ER stress, promoting protein homeostasis in the ER. ..
  8. Guna A, Hegde R. Transmembrane Domain Recognition during Membrane Protein Biogenesis and Quality Control. Curr Biol. 2018;28:R498-R511 pubmed publisher
    ..Here, we discuss the growing assortment of cytosolic and membrane-embedded TMD-recognition factors, the pathways within which they operate, and mechanistic principles of recognition. ..
  9. Voorhees R, Hegde R. Toward a structural understanding of co-translational protein translocation. Curr Opin Cell Biol. 2016;41:91-9 pubmed publisher
    ..These advances are being utilized to obtain near-atomic resolution reconstructions of functional translation, targeting, and translocation intermediates, paving the way to a mechanistic understanding of protein biogenesis. ..

More Information


  1. 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. ..
  2. 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. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. 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. ..
  7. Shao S, Brown A, Santhanam B, Hegde R. Structure and assembly pathway of the ribosome quality control complex. Mol Cell. 2015;57:433-44 pubmed publisher
  8. 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. ..
  9. 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. ..
  10. 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. ..
  11. 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. ..