Infrared spectroscopy of proteins.

This review deals with current concepts of vibrational spectroscopy for the investigation of protein structure and function. While the focus is on infrared (IR) spectroscopy, some of the general aspects also apply to Raman spectroscopy. Special emphasis is on the amide I vibration of the polypeptide backbone that is used for secondary-structure analysis. Theoretical as well as experimental aspects are covered including transition dipole coupling. Further topics are discussed, namely the absorption of amino-acid side-chains, 1H/2H exchange to study the conformational flexibility and reaction-induced difference spectroscopy for the investigation of reaction mechanisms with a focus on interpretation tools.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033583502003815

What vibrations tell us about proteins

Ordered protein aggregation in the brain is a hallmark of Alzheimer's disease and scrapie. The disease-specific amyloid fibrils comprise primarily a single protein, amyloid beta, in Alzheimer's disease, and the prion protein in scrapie. These proteins can be induced to form aggregates in vitro that are indistinguishable from brain-derived fibrils. Consequently, much effort has been invested in the development of in vitro model systems to study the details of the aggregation processes and the effects of endogenous molecules that have been implicated in disease. Selected studies of this type are reviewed herein. A simple mechanistic model has emerged for both processes that involves a nucleation-dependent polymerization. This mechanism dictates that aggregation is dependent on protein concentration and time. Furthermore, amyloid formation can be seeded by a preformed fibril. The physiological consequences of this mechanism are discussed.

MODELS OF AMYLOID SEEDING IN ALZHEIMER'S DISEASE AND SCRAPIE: Mechanistic Truths and Physiological Consequences of the Time-Dependent Solubility of Amyloid Proteins

Amyloid fibrils commonly exhibit multiple distinct morphologies in electron microscope and atomic force microscope images, often within a single image field. By using electron microscopy and solid-state nuclear magnetic resonance measurements on fibrils formed by the 40-residue beta-amyloid peptide of Alzheimer's disease (Abeta(1-40)), we show that different fibril morphologies have different underlying molecular structures, that the predominant structure can be controlled by subtle variations in fibril growth conditions, and that both morphology and molecular structure are self-propagating when fibrils grow from preformed seeds. Different Abeta(1-40) fibril morphologies also have significantly different toxicities in neuronal cell cultures. These results have implications for the mechanism of amyloid formation, the phenomenon of strains in prion diseases, the role of amyloid fibrils in amyloid diseases, and the development of amyloid-based nano-materials.

http://science.sciencemag.org/content/sci/307/5707/262.full.pdf

Self-Propagating, Molecular-Level Polymorphism in Alzheimer's ß-Amyloid Fibrils

SIMPSON: a general simulation program for solid-state NMR spectroscopy.

Amyloids are a class of noncrystalline, yet ordered, protein aggregates. A new approach was used to provide the initial structural data on an amyloid fibril—comprising a peptide (β34–42) from the C-terminus of the β-amyloid protein—based on measurement of intramolecular 13C–13C distances and 13C chemical shifts by solid-state 13C NMR and individual amide absorption frequencies by isotope-edited infrared spectroscopy. Intermolecular orientation and alignment within the amyloid sheet was determined by fitting models to observed intermolecular 13C–13C couplings. Although the structural model we present is defined to relatively low resolution, it nevertheless shows a pleated antiparallel β-sheet characterized by a specific intermolecular alignment.

Structural model for the β-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide

We discuss several aspects of homonuclear recoupling and longitudinal exchange using rotor-synchronized spin echo sequences in solid state magic-angle spinning (MAS) experiments. These include the accurate measurement of weak dipole–dipole couplings between rare spins, the behavior of dipolar trajectories in multiple spin environments, and chemical shift correlation spectroscopy via polarization exchange. To describe dipolar trajectories accurately, we adopt an approach to the simulation of these experiments which includes finite pulses and the influence of coherence decay. The latter effect becomes competitive with the strength of weak couplings in many experiments, and a simple empirical approach is outlined for the selection of decay parameters. Dipolar trajectories are shown to be dominated by the largest couplings in multiple spin systems via comparison of two and three interacting spins. Two-dimensional correlation spectroscopy based on dipolar exchange among proximate nuclei is illustrated with a uniformly 15N,13C-labeled sample of the tetrapeptide achatin-II (Gly-L-Phe-L-Ala-L-Asp). In addition, a frequency-selective approach to recoupling dipolar interactions among homonuclear spins is introduced; selective approaches have possible utility in examining weak dipole–dipole couplings in the presence of strong interactions.

Janet M. Griffiths

Papers

Structural model for the β-amyloid fibril based on interstrand alignment of an antiparallel-sheet comprising a C-terminal peptide

Homonuclear radio frequency-driven recoupling in rotating solids

Rotational Resonance Solid-State NMR Elucidates a Structural Model of Pancreatic Amyloid

Nuclear magnetic resonance methods for measuring dipolar couplings in rotating solids

Dipolar Correlation NMR-Spectroscopy of a Membrane-Protein