NMR Spectroscopy for Probing Functional Dynamics at Biological Interfaces

Cover
Preface
Contents
Chapter 1 Theory and Applications of NMR Spectroscopy in Biomolecular Structures and Dynamics of Proteins
1.1 Introduction
1.2 Methodologies Involving Protein Structure Determination: A Comparative Study
1.3 Through Space Correlation
1.3.1 Nuclear Overhauser Effect
1.4 Summary and Future Perspectives
List of Abbreviations
References
Chapter 2 Multistate Structures and Dynamics at Atomic Resolution Using Exact Nuclear Overhauser Enhancements (eNOEs)
2.1 Introduction
2.2 Results and Discussion
2.2.1 Exact Nuclear Overhauser Effect Spectroscopy
2.2.2 Multistate Ensemble Structure Determination (Using eNOEs)
2.2.3 Recent Applications of Exact Nuclear Overhauser Enhancement
2.3 Conclusion
References
Chapter 3 Protein Backbone and Side-chain 15N Spin Relaxation Techniques to Study Biomacromolecular Interactions
3.1 Molecular Dynamics: Time Scales of Motions in Proteins
3.2 NMR Available Observables Dependent on Molecular Motions: Relaxation Rates
3.3 The Protein Backbone and Side-chains Accessible
via 15N Spins
3.4 Motional Models Commonly Used in Proteins: MFA/EMFA, SDM
3.5 Determination of Model Parameters Based on Observables
3.6 Unstructured Proteins or Their Parts
3.7 Biomaterial Preparation for 15N Spin Relaxation
Studies
3.8 Practical Considerations of Experimental Setup and Dedicated Pulse Programmes
3.9 Perspectives and Future Development
References
Chapter 4 Lineshape Analysis as a Tool for Probing Functional Motions at Biological Interfaces
4.1 Introduction
4.2 Theoretical Background
4.2.1 NMR Lineshape is a Lorentzian Function
Defined by R2 (Peak Linewidth) and
Chemical Environment (Peak Frequency)
4.2.2 Exchange Between Different Chemical Environments Alters Lineshape
4.2.3 Mathematical Framework for Simulating Lineshape
4.2.4 Independent Measurements to Reduce the Number of Fitted Parameters in the Four-state Model
4.2.5 Independent Measurements to Provide Validation of Fitted Parameters for the Four-state Model
4.2.6 Extracting Exchange Parameters (Rates, Populations) from Lineshapes
4.3 Applications of Lineshape Analysis
4.3.1 Complete Characterization of Pin1 Catalysis of APP Substrate
4.3.2 Characterization of the Reaction Cycle
Parameters for Cyclophilin LRT2/Cyp2
Acting on Transcription Repressor OsIAA11
in Rice
4.4 Conclusions and Perspectives
Acknowledgements
References
Chapter 5 Monitoring Interfaces of Thermoand pH-responsive Polymers Using Solvent Relaxation
5.1 Introduction
5.1.1 Solvent Relaxation Method
5.1.2 Interfaces of Smart Polymers
5.1.3 Relaxation Dispersion and Chemical Exchange
5.2 Exchanges at the Interface of Micellar Aggregates
5.2.1 The Model and the Method
5.2.2 Results
5.3 Thermal Mixing: Coil-to-globule Transitions
5.3.1 The Model and the Method
5.3.2 Results
5.4 Summary and Outlook
References
Chapter 6 NMR-based Ligand–Receptor Interaction Studies under Conventional and Unconventional Conditions
6.1 Introduction
6.2 NMR Molecular Recognition Techniques Based on Ligand Resonance Observation
6.2.1 Brief Description of the Main Experiments Based on Ligand-resonance Observation
6.2.2 Solvent Saturation Transfer
6.2.3 Transferred NOESY (trNOESY)
6.2.4 Diffusion Coefficient Measurements
6.2.5 Relaxation Time Measurements
6.3 NMR Interaction Studies on Complex Compound Mixtures
6.3.1 NMR-based Screening of Libraries of Synthetic Compounds
6.3.2 NMR-based Screening of Complex Mixtures of Natural Compounds
6.3.3 A Brief Resume of the Advantages and Disadvantages (and How to Overcome Them) of Studies on Ligand Mixtures
6.4 NMR Interaction Studies Involving Multivalent Ligands, Liposomes, Nanoparticles and Peptide/Protein Aggregates
6.5 On-cell NMR Molecular Recognition Studies
6.6 Final Remarks
Acknowledgements
References
Chapter 7 Multi-frequency Saturation Transfer Difference NMR
to Characterize Weak Protein–Ligand Complexes
7.1 Introduction
7.1.1 Weak Protein–Ligand Interactions
7.1.2 The Role of NMR Spectroscopy
7.2 Saturation Transfer Difference NMR
7.2.1 Theoretical Concepts
7.2.2 STD NMR Sample Preparation and Pulse Sequences
7.2.3 Qualitative and Semi-quantitative STD NMR: Ligandbinding Epitope Mapping
7.2.4 Quantitative STD NMR: CORCEMA-ST Approach; Analysis of Multi-modal Binding
7.3 Multi-frequency STD NMR
7.3.1 Differential Epitope Mapping STD NMR (DEEP-STD NMR)
7.4 Summary and Conclusions
References
Chapter 8 Structural Insight into the Slowly Exchanging Dark States at the Functional Interaction Interface
8.1 Introduction
8.2 Probing the Dynamicity of Functional Conformers
8.3 Relaxation in Studying Protein Dynamics
8.4 Chemical Exchange at the Functional Interface
8.5 Characterizing Chemical Exchange Between an NMR-visible and Invisible State
8.6 Basic Principle of Applying Saturation Transfer: Characterizing the ‘‘Dark’’ Species
8.7 Dark-state Exchange Saturation Transfer: The Standing Principle
8.8 Description of the 2D 15N-DEST Experiment and
Pulse Sequence
8.9 Quantifying the Chemical Exchange
8.10 Applications
8.10.1 Probing the Atomic-resolution Nucleation Events in Ab Amyloidogenesis
8.10.2 Qualitative Insight into the Interaction Interfaces
8.11 Experimental Sample Conditions are Critical for DEST Analysis
8.12 Conclusions
Acknowledgements
References
Chapter 9 Dynamics of Protein–Nanoparticle Interactions Using NMR
9.1 Introduction
9.2 Characterization of Protein–NP Interactions by Various Techniques
9.3 Solution NMR Spectroscopy to Understand Protein–Nanoparticle Interactions
9.4 Protein–NP Systems Investigated by Solution NMR Spectroscopy
9.4.1 Noble Metal Nanoparticles (AuNPs and AgNPs)
9.4.2 Carbon-based Nanoparticles
9.4.3 Silica Nanoparticles
9.5 Therapeutic Approaches to Protein–NP Interactions
9.6 Conclusion and Future Prospects
Acknowledgements
References
Chapter 10 NMR Structures, Dynamics and Interactions of Protein Complexes in b2 Integrins
10.1 Integrins: An Overview
10.2 The Cytosolic Tails (CTs) of Integrins
10.3 The Cytosolic Tails of β2 Integrins: Structures
and Interactions
10.4 Structures and Interactions between αM, αX and β2 CTs
10.5 Structures and Interactions of β Cytosolic Tails with Effector Proteins
10.6 Concluding Remarks
Acknowledgements
References
Chapter 11 Describing Dynamic Chaperone–Client Complexes by Solution NMR Spectroscopy
11.1 Introduction
11.2 NMR Techniques for Chaperone–Client Complexes
11.2.1 Determination of Spatial Contacts Between Client and Chaperone
11.2.2 Intramolecular Client Contacts
11.2.3 Lifetime of Chaperone–Client Complexes
11.2.4 Dynamics of the Client
11.2.5 Dynamics of the Chaperone
11.2.6 Structural Modeling
11.3 Conclusion and Outlook
References
Chapter 12 Methyl-TROSY NMR Spectroscopy in the Investigation of Allosteric Cooperativity in Large Biomolecular Complexes
12.1 Introduction
12.2 Cooperativity
12.2.1 What Is Cooperativity?
12.2.2 Biological Significance of Allosteric Cooperativity
12.2.3 Classical Models of Cooperativity: MWC and KNF Models
12.3 Cooperativity of Conformational Interconversion in the Absence of Ligand
12.3.1 Coupled Conformational Exchange
12.3.2 Strategies to Probe Conformational Cooperativity
12.3.3 Reconstitution of Hetero-oligomers and Differential Isotope Labeling
12.3.4 Cooperativity Described by Conditional Probabilities
12.4 Methyl-TROSY
12.4.1 Overview of Methyl-TROSY
12.4.2 Isotope Labeling of Methyl Groups
12.4.3 Assignment of Methyl Resonances
12.5 Application of Methyl-TROSY in the Investigation of Cooperativity in Large Protein Complexes
12.5.1 Cooperative Gating of Archaeal 20S Proteasome
12.5.2 Cooperative Domain Dynamics in p97
12.5.3 A Highly Cooperative N-terminal Conformational Switch in SaClpP
12.5.4 Cooperative Activation of mtClpP1P2
12.6 Conclusions and Outlook
Acknowledgements
References
Chapter 13 Characterizing Conformational Diversity of G Protein-coupled Receptors by Solution NMR Spectroscopy
13.1 Introduction
13.1.1 Overview of GPCR Structure
13.1.2 Structural Rearrangement of GPCRs upon Activation
13.2 Preparing GPCRs for NMR Spectroscopy
13.2.1 Expression Systems
13.2.2 Isotope-labelling and Assignment Strategies
13.2.3 Membrane Mimetic Systems
13.3 Receptor-observed NMR Spectroscopy
13.3.1 β2-AR
13.3.2 β1-AR
13.3.3 A2AAR
13.3.4 µOR
13.3.3 A2AAR
13.3.5 Other GPCRs, M2R, α1A-AR, NTS1 and BLT2
13.3.6 Complexes of GPCRs and Heterotrimeric Gαβϒ Proteins
13.4 Ligand-observed NMR Studies of GPCRs
13.4.1 Small-molecule Ligands
13.4.2 Peptide Ligands
13.5 Conclusions
References
Chapter 14 Characterising Intrinsically Disordered Proteins Using NMR Spectroscopy and MD Simulations
14.1 Introduction
14.2 NMR Spectroscopy to Characterise IDPs
14.2.1 Chemical Shifts and the Fingerprints of IDPs
14.2.2 Information on Residual Structure
14.2.3 Other NMR Observables
14.2.4 Characterising Conformational and Chemical Exchange
14.2.5 Ensemble Description Methods without MD
14.3 MD Simulations of IDPs
14.3.1 Force Fields for IDPs: Bottlenecks and Progress
14.3.2 The Sampling Problem and Solutions for IDPs
14.3.3 Other MD Approaches for Characterising Protein Disorder
14.4 Integrative Modelling of IDPs by Combining NMR and MD
14.4.1 Comparing MD Ensembles with NMR Observables
14.4.2 Maximum Entropy versus Maximum
Parsimony Methods
14.4.3 Accounting for Errors with Bayesian Inference
14.5 Conclusion and Future Perspectives
Acknowledgements
References
Chapter 15 Structure- and Dynamics-guided Drug Development Using
NMR and its Application to Diverse Pharmaceutical
Modalities
15.1 Introduction
15.2 NMR Techniques to Promote the Use of New Pharmaceutical Modalities
15.3 NMR Characterization of HMW Biopharmaceuticals
15.3.1 Limitation of Conventional and 1D NMR in the HOS Analyses of HMW Biopharmaceuticals
15.3.2 Variable-temperature NMR Experiments
15.3.3 Application of 15N-direct Observation to
HOS Analyses of HMWBiopharmaceuticals
15.3.4 19F–13C TROSY Measurement Technique
15.4 Dynamic Structural Optimization of Ligands, Including Medium-size Molecules
15.4.1 Utilization of Forbidden Coherence Transition (FCT) for Dynamic Ligand Optimization
15.4.2 Consideration of Multiple Binding Modes in Ligand Optimization
15.5 Controlling the Dynamics of a Target Protein to Facilitate SGDD
15.6 Kinetics Parameter of Interaction by NMR Dynamics Analysis
15.7 Elucidation of Cell Permeabilization Activity of Medium-size Molecules by NMR
15.8 Conclusion
Abbreviations
Acknowledgements
References
Chapter 16 Locating Hydrogen Atoms Using Fast-MAS Solid-state NMR and microED
16.1 Introduction
16.2 Heteronuclear Dipolar Interactions
16.2.1 REDOR, DIPSHIFT and Related Methods: Working Principle
16.2.2 DIPSHIFT
16.2.3 Heteronuclear Dipolar Coupling Measurements Using Magnetization Transfer
16.3 Homonuclear Dipolar Coupling
16.4 Electron and NMR Crystallography
16.5 Summary
Acknowledgements
References
Chapter 17 Membranes, Minerals and Magnets: Application of NMR Spectroscopy to Biological Interfaces
17.1 Introduction
17.2 Membranes and Membrane Proteins
17.2.1 Detergent Micelles
17.2.2 Detergent-free Lipid Bilayers
17.3 Biominerals
17.3.1 Protein–Metal Ion Interactions in Solution
17.3.2 Protein–Hydroxyapatite Interactions
17.3.3 Moving Toward Ordered Biomineral Structures
17.4 Concluding Remarks
Abbreviations
References
Chapter 18 Solid-state NMR Shows That the Structure and Dynamics
of Specific Residues in the Membrane Receptor CXCR1 Are
Altered by Interactions with Specific Residues in Its
Agonist IL-8
18.1 Introduction
18.1.1 Structure, Dynamics, and Interactions of Membrane Proteins in Lipid Bilayers
18.1.2 G Protein-coupled Receptors
18.2 Dynamics of Membrane Proteins
18.2.1 Dynamics by Solid-state NMR
18.2.2 Use of Membrane Protein Dynamics in Structure Determination
18.2.3 Dynamics of CXCR1
18.3 IL-8 Interactions with CXCR1
18.3.1 Solid-state NMR Experiments
18.3.2 Interactions and Dynamics: Experimental Results
18.3.3 Discussion
Acknowledgements
References
Chapter 19 High-resolution NMR Studies of Antibiotics in Membranes
19.1 Introduction
19.2 Lipid II Modifications
19.3 Vancomycin and Other Glycopeptides
19.4 Nisin and Other Lantibiotics
19.5 Plectasin and Other CS-αβ Defensins
19.6 Teixobactin
19.7 Daptomycin
19.8 Conclusions
Abbreviations
Acknowledgements
References
Chapter 20 New Concepts for the Mechanisms of Action of Antimicrobial Peptides from Solid-state NMR Investigations
20.1 Introduction
20.1.1 Antimicrobial Peptides
20.1.2 Solid-state NMR Investigations of Polypeptides
20.2 Solid-state NMR Applications to Antimicrobial Peptides
20.2.1 Magainins and PGLa
20.2.2 Static Solid-state NMR Spectroscopy of Lipids
20.2.3 Solid-state NMR Investigations of the Synergistic Enhancements of AMP Activities
20.2.4 NMR Investigations of AMP Dimers
20.2.5 Designed Antimicrobial Model Peptides and Refinement of the Topological Analysis
20.2.6 Structural Investigations of Bilayer Lipids and of Membrane-bound Antimicrobial Peptides by MAS Solid-state NMR Spectrosc
20.2.7 Mechanistic Models for AMP Activities
20.3 Conclusions and Outlook
20.4 Materials and Methods
20.4.1 Materials
20.4.2 Sample Preparation for Oriented Solid-state NMR
20.4.3 Solid-state NMR of Oriented Samples
20.4.4 MAS Spectra of Uniformly Labelled Peptides
Abbreviations
Acknowledgements
References
Chapter 21 Structure and Dynamics of Native Biological Materials by Solid-state NMR Spectroscopy
21.1 Introduction
21.2 ssNMR Studies of Native Biological Materials
21.2.1 Bone and Cartilage
21.2.2 Dentin
21.2.3 Keratin
21.2.4 Corals and Silk
21.3 Conclusion and Future Directions
Abbreviations
Acknowledgements
References
Chapter 22 The Lipid Phase of the Stratum Corneum Studied by Solid-state NMR: A Not So Rigid Barrier
22.1 Introduction
22.2 Biophysical Methods to Study the Structure and
Dynamics of Stratum Corneum Lipid Assemblies
22.2.1 Solid-state NMR Spectroscopy
22.2.2 Other Biophysical Techniques
22.3 Results
22.3.1 The LPP Model of the Stratum Corneum:
Rigid Lipid Layer with a Highly Mobile
Core
22.3.2 The SPP Model of the Stratum Corneum: An
Interface Containing Highly Mobile Lipids
22.4 Conclusions
Abbreviations
Acknowledgements
References
Subject Index