Using a collection of modern nuclear magnetic resonance methods, the McDermott lab studies the structure, function, and conformational dynamics of proteins in native-like environments. Efforts of the research group demonstrated that NMR spectra of solid state proteins, such as membrane proteins in native lipid bilayers, or protein assemblies like viral coats, can provide well resolved spectra, structures and detailed characterization of dynamic properties. NMR studies clarify the relationship of enzymatic function to protein conformational exchange, including active site loop motions and substrate repositioning in a number of examples.
Function and Flexibility of Membrane Proteins: Ann McDermott’s research group studies the structure, flexibility and function of proteins using magnetic resonance methods. For example, we study the structure and function of potassium ion channels, which play crucial roles in diverse contexts, from bacteria to the human nervous system. Our work illuminated the role of an ion-depleted state and provided evidence for strong allosteric coupling in channel regulation, using the prototypical prokaryotic ion channel KcsA. As for many enzymes and drug targets, ligand binding is associated with internal motions. The characteristic timescales of active-site flexible loop motions in other proteins have been studied in the past by the McDermott group, and ongoing studies of the channel position us to carry out detailed dynamics of the channel.
Structures Bio Assemblies: The McDermott group has studied a number of bio-assemblies, including a virus coats and amyloids whose formation is proposed to be a critical step in cellular signaling in humans. NMR spectra of isotopically enriched proteins in the solid state can provide the basis for detailed and highly resolved structures. The development of methods for structure determination by solid state NMR remains an active area.
NMR Methods Development, Enhanced Signals, and Alignment Protocols: We study and use mechanisms to enhance NMR detection. Dynamic Nuclear Polarization studies involving affinity-attached radicals are used to achieve selective sensitization of biomolecules of interest in complex environments, such as cells. In a separate effort, we discovered that photo-excited NMR signals associated with the photosynthetic apparatus appear with intensities enhanced 300 to 1,000 times, relative to thermal polarization values, and described a mechanism for this remarkable effect. I addition, we implement new high-dimensional NMR pulse sequences to carry out assignments of NMR spectra of biopolymers at low temperature with strongly polarized NMR signals.
Bhate M.P. and McDermott A. (2012) Protonation state of E71 in KcsA and its role for channel collapse and inactivation. PNAS, 109, 15265-15270.
Li, Jixi; McQuade, Thomas; Siemer, Ansgar B.; Napetschnig, Johanna; Moriwaki, Kenta; Hsiao, Yu-Shan; Damko, Ermelinda; Moquin, David; Walz, Thomas; McDermott, Ann; Chan, Francis Ka-Ming & Wu, Hao. (2012) The RIP1/RIP3 Necrosome Forms A Functional Amyloid Signaling Complex Required for Programmed Necrosis. Cell 150, 339-350.
Raveendra, Bindu L.; Siemer, Ansgar B.; Puthanveettil, Sathyanarayanan V.; Hendrickson, Wayne A.; Kandel, Eric R. & McDermott, Ann E. (2013) Characterization of prion-like conformational changes of the neuronal isoform of Aplysia CPEB. Nature Structural & Molecular Biology, 20, 495-501.
Wylie, Benjamin J.; Bhate, Manasi P.; & McDermott, Ann E. (2014) Allostery and Channel Inactivation: Global Effects of K+ Binding on KcsA in Hydrated Bilayers. Proc. Natl. Acad. Sci. v 111, p 185-190.
Sergeyev, Ivan V. & McDermott, Ann E. (2014) Studies of Water Populations in Pf1 Bacteriophage by NMR. J. Chem. Phys. 141(22) 22D533
Wylie, Benjamin J., Dzikovski, B, Pawsey, S., Caporini, M., Rosay, M., Freed, J., & McDermott, Ann E. (2015) Dynamic Nuclear Polarization of Membrane Proteins Using Covalently Bound Radicals. Journal of Biomlecular NMR, volume 61, p 361-3
Laage, Ségolène, Tao, Yisong and McDermott, Ann E. (2015) Cardiolipin Interaction with Subunit c of ATP Synthase: Solid-state NMR Characterization, Biophys Biochem A v 1848 260-265.
Miguel Mompeán, Rubén Hervás, Yunyao Xu, Timothy H. Tran, Corrado Guarnaccia, Emanuele Buratti, Francisco Baralle, Liang Tong, Mariano Carrión-Vázquez, Ann E. McDermott, and Douglas V. Laurents (2015) Structural Evidence of Amyloid Fibril Formation in the Putative Aggregation Domain of TDP-43 J. Phys. Chem. Lett., 6 (13), pp 2608–2615.
Harris MJ, Struppe JO, Wylie BJ, McDermott AE, Thompson LK. (2016) Multidimensional Solid-State Nuclear Magnetic Resonance of a Functional Multiprotein Chemoreceptor Array. Biochemistry 55(26):3616-24.
Rogawski, Rivkah; Sergeyev, Ivan V.; Li, Yongjun; Cornish, Virginia W.; McDermott, Ann E. (2016) Dynamic Nuclear Polarization Signal Enhancement with High-Affinity Biradical Tags, Journal of Physical Chemistry B, 121 (6), 1169-1175.
Sergeyev, Ivan V.; Itin, Boris; Rogawski, Rivkah; Day, Loren A.; McDermott, Ann E. (2017) Efficient Assignment and NMR Analysis of an Intact Virus Using Sequential Sidechain Correlations and DNP Sensitization, PNAS 114 (20), 5171-5176.
Xu, Yunyao; Bhate, Manasi P.; McDermott, Ann E. (2017) Transmembrane Allosteric Energetics: Strong coupling between protons and potassium ions binding in the KcsA channel, PNAS 114 (33) 8788-8793.
Rogawski, Rivkah; McDermott, Ann E. (2017) New NMR Tools for Protein Structure and Function: Spin Tags for Dynamic Nuclear Polarization Solid State NMR. Arch Biochem. Biophys. 628 102-113.
Rogawski, Rivkah; Sergeyev, Ivan V.; Li, Yongjun; Tong, Liang; McDermott, Ann E. (2017) NMR Signal Quenching from Bound Biradical Affinity Reagents in DNP, Journal of Physical Chemistry, in press.
Fritzsching, K., Itin, B, and McDermott, A. (2017) N,N-Diethylmethylamine as lineshape standard for NMR above 130 K, JMR, in press.
McDermott, Ann E. (Ed.), Polenova, Tatyana (Ed.) Solid State NMR Studies of Biopolymers. West Sussex, UK: John Wiley & Sons, 2010. ISBN: 978-0-470-72122-3