Download or read book Solid state Nuclear Magnetic Resonance Investigations of the Influenza M2 Protein written by Jonathan Kyle Williams and published by . This book was released on 2017 with total page 224 pages. Available in PDF, EPUB and Kindle. Book excerpt: Solid-state nuclear magnetic resonance (ssNMR) spectroscopy is a powerful technique that can be used to probe the structure and dynamics of biomolecules that are intractable to study by other structural biology methods. In this thesis, the mechanisms of conduction and gating are investigated in the influenza AM2 and BM2 proton channels bound to native-like lipid bilayers. Using pH-dependent 15N chemical shifts of the conserved Histidine residue, we have found that the proton conduction mechanism is the same in all of the M2 channels (WT AM2, S3 IN AM2, BM2) studied, and that the conduction cycle involves proton shuttling via hydrogen-bonding with water. For the first time, unambiguous structural restraints and sidechain dynamics were measured for the gating residue Trp4l in the AM2 channel. Trp4l was found to come into close contact with His37, close enough to undergo periodic cation-[pi] interactions that ensure unidirectional proton flow. Water-edited 1H-13C correlation experiments were used to investigate the channel hydration of AM2 and BM2 tetramers, and S12 in the C-terminal BM2 channel was found to have the largest pH-dependent spin-diffusion buildup of all residues studied, indicating that the BM2 serine triplet plays an important role in conduction. New ssNMR methods were developed to probe long-range 13C-13C distances, and to edit and clean-up crowded spectra of peptides and proteins containing aromatic residues. The ASSET technique removes the aliphatic cross peaks of all residues except for Phe, Trp, Tyr, and His in a two-dimensional 13C-13C correlation experiment, while a two-dimensional 13C-13C correlation experiment with gated-decoupling retains only non-protonated 3C resonances. The studies in this thesis have provided insight into the functionally important His and Trp residues in the M2 proton channel of the influenza virus, and provide new avenues for studying other peptides and proteins containing aromatic residues.
Download or read book Investigation of the Structure and Dynamics of the M2 Transmembrane Peptide of the Influenza A Virus by Solid state Nuclear Magnetic Resonance written by Sarah Diane Cady and published by . This book was released on 2009 with total page 259 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structural Characterization of the M2 Protein Ion Channel of the Influenza A Virus Using Solid State Nuclear Magnetic Resonance Spectroscopy written by Frank A. Kovacs and published by . This book was released on 1999 with total page 234 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Solid State Nuclear Magnetic Resonance Studies of the Influenza Fusion Peptide Associated with Membrane Bilayers written by Paul Parkanzky and published by . This book was released on 2006 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structure and Dynamics of Full length M2 Protein of Influenza A Virus from Solid state NMR written by Shu-Yu Liao (Ph. D.) and published by . This book was released on 2017 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt: Solid-state nuclear magnetic resonance (SSNMR) has been frequently used to elucidate the structure and dynamics of membrane proteins and fibrils that are difficult to characterize by Xray crystallography or solution NMR. This thesis focuses on the structure determination and the proton conduction mechanism of the full-length matrix protein 2 (M2) of influenza A virus. The M2 membrane protein can be separated into three domains: an N-terminal ectodomain (1-2 1), an cc-helical transmembrane domain (TM) (22-46) connected to an amphipathic helix (AH) and a Cterminal cytoplasmic tail (63-97). The TM domain of M2 is responsible for proton conduction ant the ectodomain has been the target for vaccine development. The cytoplasmic tail has been implicated in M2 interaction with other viral proteins from mutagenesis studies. Given the importance of both N- and C-termini, it is essential to determine the structure and the dynamics of M2FL. Furthermore, we are interested in how the cytoplasmic tail affects proton conduction and the interaction of the anti-viral drug amantadine with M2 in the presence of the C-terminus. Using uniformly 13C, 15N-labeled M2FL, our water-selected 2D 13C-13C correlation experiment indicated that N- and C- termini are on the surface of the lipid bilayer moreover combining with chemical shift prediction, we determined that these two domains are mostly disordered. Deleting the ectodomain of M2FL (M2(21-97)) proved that a small [beta]-strand is located at the N-terminus only in the DMPC-bound state. The M2 conformation is found to be cholesterol-dependent since [beta]-strand is not found in cholesterol-rich membranes. M2(21-97) shows cationic histidine at higher pH, in contrast to M2TM, indicating that the cytoplasmic tail shifts the His37 pKa equilibria. Quantification of the 15N intensities revealed two pKa's as opposed to of four in M2TM suggesting cooperative proton binding. A possible explanation is that the large number of positively charged residues in the cytoplasmic tail facilitates proton conduction. The cytoplasmic tail was also found to restore drug-binding as amantadine no longer binds to M2(21-61) a in virus-mimetic membrane. These results have extended our understanding of the influence of the cytoplasmic domain on the structure and proton conduction of M2.
Download or read book An Investigation of the Protonation of Histidine 37 in Influenza A Virus M2 Protein by Solid State NMR written by Li Zhang and published by . This book was released on 1998 with total page 198 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Structural and Dynamics Characterization of Membrane Proteins Using Static Solid state Nuclear Magnetic Resonance Spectroscopy written by Conggang Li and published by . This book was released on 2007 with total page 116 pages. Available in PDF, EPUB and Kindle. Book excerpt: Solid-state nuclear magnetic resonance (NMR) provides a unique approach for structure determination and functional studies of membrane proteins in a native lipid bilayer environment. Here, polarization inversion spin exchange at magic angle (PISEMA) experiments of aligned samples were applied to study the proton channel, M2 protein transmembrane portion (M2-TMD) from influenza A virus and other intact full length membrane proteins. The challenges of membrane protein structure characterization utilizing static aligned sample, including sample preparation, sample stability induced by RF heating, PISEMA experiment set up were discussed.
Download or read book Solid State NMR Spectroscopy written by Melinda J. Duer and published by John Wiley & Sons. This book was released on 2008-04-15 with total page 592 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is for those familiar with solution-state NMR who are encountering solid-state NMR for the first time. It presents the current understanding and applications of solid-state NMR with a rigorous but readable approach, making it easy for someone who merely wishes to gain an overall impression of the subject without details. This dual requirement is met through careful construction of the material within each chapter. The book is divided into two parts: "Fundamentals" and "Further Applications." The section on Fundamentals contains relatively long chapters that deal with the basic theory and practice of solid-state NMR. The essential differences and extra scope of solid-state NMR over solution-state is dealt with in an introductory chapter. The basic techniques that all chapters rely on are collected into a second chapter to avoid unnecessary repetition later. Remaining chapters in the "Fundamentals" part deal with the major areas of solid-state NMR which all solid-state NMR spectroscopists should know about. Each begins with an overview of the topic that puts the chapter in context. The basic principles upon which the techniques in the chapter rely are explained in a separate section. Each of these chapters exemplifies the principles and techniques with the applications most commonly found in current practice. The "Further Applications" section contains a series of shorter chapters which describe the NMR techniques used in other, more specific areas. The basic principles upon which these techniques rely will be expounded only if not already in the Fundamentals part.
Download or read book Solid State Nuclear Magnetic Resonance Studies of Prion Peptides and Proteins written by Jonathan Heller and published by . This book was released on 1997 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Solid state Nuclear Magnetic Resonance Studies of the Major Coat Protein from the Filamentous Bacteriophage Fd written by Ana Carolina de Mattos Zeri and published by . This book was released on 2003 with total page 262 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Solid State Nuclear Magnetic Resonance of the HIV 1 and Influenza Fusion Peptides Associated with Membranes written by Michele L. Bodner and published by . This book was released on 2006 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Nuclear Magnetic Resonance written by Krystyna Kamienska-Trela and published by Royal Society of Chemistry. This book was released on 2015-05-20 with total page 638 pages. Available in PDF, EPUB and Kindle. Book excerpt: Applications of nuclear magnetic resonance span a wide range of scientific disciplines, from physics to medicine. This series has provided an essential digest of the NMR literature for more than four decades and each volume provides unrivalled coverage of the literature on this topic. Continuous coverage on some topics such as theoretical and physical aspects of nuclear shielding is balance by the desire for coverage on newer topics like applications in biological systems and materials science. For those wanting to become rapidly acquainted with NMR or seasoned practitioners, this is an invaluable source of current methods and applications.
Download or read book Secondary Structure and Membrane Insertion of the Membrane associated Influenza Fusion Peptide Probed by Solid state Nuclear Magnetic Resonance written by Yan Sun and published by . This book was released on 2009 with total page 484 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Nuclear Magnetic Resonance written by G A Webb and published by Royal Society of Chemistry. This book was released on 2008-05-27 with total page 387 pages. Available in PDF, EPUB and Kindle. Book excerpt: As a spectroscopic method, nuclear magnetic resonance (NMR) has seen spectacular growth over the past two decades, both as a technique and in its applications. Today the applications of NMR span a wide range of scientific disciplines, from physics to biology to medicine. Each volume of Nuclear Magnetic Resonance comprises a combination of annual and biennial reports which together provide comprehensive coverage of the literature on this topic. This Specialist Periodical Report reflects the growing volume of published work involving NMR techniques and applications, in particular NMR of natural macromolecules which is covered in two reports: "NMR of Proteins and Nucleic Acids" and "NMR of Carbohydrates, Lipids and Membranes". For those wanting to become rapidly acquainted with specific areas of NMR, this title provides unrivalled scope of coverage. Seasoned practitioners of NMR will find this an invaluable source of current methods and applications. Volume 37 covers literature published from June 2006 to May 2007.
Download or read book Nuclear Magnetic Resonance written by and published by Royal Society of Chemistry. This book was released on 2014-05-21 with total page 569 pages. Available in PDF, EPUB and Kindle. Book excerpt: Now in its 43rd volume, the Specialist Periodical Report in Nuclear Magnetic Resonance presents comprehensive and critical reviews of the recent literature, providing the reader with an informed summary of the field from invited authors. Several chapters in this volume are devoted to biochemistry, focussing on carbohydrates, lipids, and proteins and nucleic acids; Malcolm Prior also presents a chapter examining the recent literature of NMR in living systems and Cynthia Jameson reviews the theoretical and physical aspects of nuclear shielding, while Jaroslaw Jazwinski examines the theoretical aspects of spin-spin couplings. The lead volume editor, Krystyna Kamienska-Trela, presents a chapter on the applications of spin-spin couplings. Anyone wishing to update themselves on the recent and hottest developments in NMR will benefit from this volume, which deserves a place in any library or NMR facility. Purchasers of the print edition can register for free access to the electronic edition by returning the enclosed registration card.
Download or read book Structure and Dynamics of Influenza M2 Proton Channels from Solid state NMR written by Venkata Shiva Mandala and published by . This book was released on 2021 with total page 229 pages. Available in PDF, EPUB and Kindle. Book excerpt: The A and B strains of influenza virus places a substantial burden on health, causing around 30 million illnesses, several hundred thousand hospitalizations, and a few tens of thousands of deaths every year in the United States alone. Developing novel antiviral and vaccines against influenza requires understanding the proteins employed by these infectious virions. The matrix-2 protein (M2) is an essential viral protein that conducts protons in the endosomes of infected host cells and induces membrane curvature to facilitate virus budding. M2’s proton channel activity is encapsulated by a transmembrane domain (TM) that is targeted by the FDA-approved antiviral drugs amantadine and rimantadine to inhibit viral replication. Proton conduction by M2’s TM is mediated by a His-xxx-Trp motif conserved in the otherwise disparate M2 from influenza A (AM2) and influenza B (BM2) strains. The histidine selects for protons and activates the channel at low pH, while the tryptophan is responsible for gating and unidirectional conduction from the N-terminus (outside) to the C-terminus (inside). M2 conducts protons across lipid bilayers at a moderate rate of ca. 10-1000 s−1. AM2 is well characterized and several high-resolution structures in a variety of membrane and membrane-mimetic environments are available, yet the mechanism of gating and the rate-limiting step of proton conduction are unknown. A gating-deficient mutant was utilized to determine that asymmetric conduction in AM2 is due to tryptophan blocking activation of histidine from the C-terminal side under low pH. Further, in phospholipid bilayers, AM2 shows two discrete conformations that interconvert on the proton conduction timescale, providing the first experimental evidence for a transporter-like mechanism. In contrast to AM2, BM2 is relatively poorly studied and no high-resolution structures in membranes is available. BM2 shares little sequence homology with AM2, is not inhibited by the antiviral drugs targeting influenza, and conducts protons faster but more bidirectionally than AM2. The first high-resolution structures of membrane-embedded BM2 in the closed and open states are reported. In contrast to the transporter-like motion of AM2, BM2 undergoes a subtler channel-like scissor opening motion, that allows for more efficient proton conduction at the expense of some bidirectional current.
Download or read book Solid State Nuclear Magnetic Resonance Studies of Model Biological Membranes written by Jose Silva Santos and published by . This book was released on 2001 with total page 448 pages. Available in PDF, EPUB and Kindle. Book excerpt:
