Structural Studies Of DNA and RNA Transactions

Our studies of nucleic acid transactions have been most powerful at defining the overall architecture of a large number of macromolecular assemblies involved in the critical initiation steps in DNA replication, RNA transcription and translation, for which no crystallographic information yet exist (e.g. ORC, TFIID, eIF3), as well as putting the crystal structures of essential elements in RNA processing and degradation in the complex of fully functional complexes (e.g. exosome, RLC). Our aim is to gain mechanistic insight that goes beyond overall architecture, by pushing resolution, describing conformational landscapes, and relating structural states to function via the analysis of interactions with ligands and regulatory factors.

Eukaryotic DNA Replication

During cell division, initiator proteins target and bind to DNA replication origins to trigger genome duplication. We are characterizing the structure of Drosophila melanogaster Origin Recognition Complex (DmORC), and the effect of nucleotide and phosphorylation state in conformation and function ... read more about ORC ...


Eukaryotic Transcription

Regulated gene transcription in eukaryotes requires the assembly of a complex molecular machinery that includes general factors, activators, cofactor complexes and chromatin modifying and remodeling factors. We are interested in characterizing the structure of these different components and how they interact to regulate transcription. Read more about chromatin remodelers ...   Read more about TFIID ...   Read more about RNAPII...   Read more about PRC2...


Eukaryotic Translation Initiation

In eukaryotes at least twelve translation initiation factors and an mRNA methylated G-cap are required to initiate protein synthesis, while in many viruses a structured RNA element replaces most of those factors. We are studying the molecular interplays that characterize both initiation pathways ... read more about eIF3


Transcription-Coupled DNA Repair

Our lab is part of a large NCI funded project in Structural Biology of DNA Repair that aims at producing biologically relevant DNA repair structures and identifying fundamental structural principles for repair proteins. The role of electron microscopy is to provide structures of large macromolecular complexes involved in these processes... read more


Recent publications

Liu JJ et al. <a href=https://www.nature.com/articles/s41586-019-0908-x> CasX enzymes comprise a distinct family of RNA-guided genome editors </a> Nature 2019 Feb 04 Patel et al. <a href=http://science.sciencemag.org/content/early/2018/11/14/science.aau8872> Structure of human TFIID and mechanism of TBP loading onto promoter DNA </a> Science 2018 Nov 15 Kellogg et al. <a href=http://science.sciencemag.org/content/early/2018/05/09/science.aat1780?rss=1> Near-atomic model of microtubule-tau interactions </a> Science 2018 May 10 Nguyen et al. <a href= https://www.nature.com/articles/s41586-018-0062-x>  Cryo-EM structure of substrate-bound human telomerase holoenzyme.
</a> Nature 2018 Apr 25 Poepsel et al. <a href=https://www.nature.com/articles/s41594-018-0023-y > Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes. </a> Nature Structural and Molecular Biology 2018 Jan 29 Kasinath et al. <a href=http://science.sciencemag.org/content/early/2018/01/17/science.aar5700 > Structures of human PRC2 with its cofactors AEBP2 and JARID2. </a> Science 2018 Jan 18 Haloupek et al. <a href=http://science.sciencemag.org/content/358/6365/888 > The structural basis of flagellin detection by NAIP5: a strategy to limit pathogen immune evasion. </a> Science 2017 Nov 17 Zhang et al. <a href=https://elifesciences.org/articles/30959 > Structural Insight into TPX2-Stimulated Microtubule Assembly.</a> Elife 2017 Nov 9 Greber et al.  <a href=https://www.ncbi.nlm.nih.gov/pubmed/28902838\ > The cryo-electron microscopy structure of human transcription factor IIH. </a><i> Nature </i>, 2017 Sep 21;549(7672):414-417 Wright AV, Liu JJ et al. <a  href=https://www.ncbi.nlm.nih.gov/pubmed/28729350\ > Structures of the CRISPR genome integration complex. </a>
Science 2017 Sep 15 Kellogg et al. <a href=http://www.sciencedirect.com/science/article/pii/S0022283617300153\> Insights into the Distinct Mechanisms of Action of Taxane and Non-Taxane Microtubule Stabilizers from Cryo-EM Structures</a><i> Journal of Molecular Biology</i>, 2017 Mar 10 He et al. <a href=https://www.ncbi.nlm.nih.gov/pubmed/27193682\> Near-atomic resolution visualization of human transcription promoter opening</a><i> Nature</i>, 2016 May 11 Louder et al. <a href=http://www.ncbi.nlm.nih.gov/pubmed/27007846> Structure of promoter-bound TFIID and model of human pre-initiation complex assembly</a><i> Nature</i>, 2016 Mar 23;531(7596):604-9 Jiang and Taylor et al. <a href=http://www.ncbi.nlm.nih.gov/pubmed/26841432> Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage.</a> <i>Science</i>, Jan 2016 Nogales and Zhang<a href=http://www.sciencedirect.com/science/article/pii/S0959440X16000038> Visualizing microtubule structural transitions and interactions with associated proteins</a> <i>COSB</i>, April 2016; <b>37</b>, 90-96 Zhang et al. <a href=http://www.sciencedirect.com/science/article/pii/S0092867415008491> Mechanistic origin of microtubule dynamic instability and its modulation by EB proteins</a><i> Cell 2015 Aug 13;162(4):849-59

Lab Member, Kelly Nguyen , will be starting as a Group Leader at the MRC-Laboratory of Molecular Biology in Cambridge, UK in August 2019

Lab member, Simon Poepsel, will be starting an Independent Research Group at the Center for Molecular Medicine at the University of Cologne, Germany in June 2019

Eva Nogales is the 2019 recipient of the Grimwade Medal