Chemistry Reference
In-Depth Information
Protein Structure Determination by
Solid-State NMR
Xin Zhao
Abstract Membrane proteins are a large, diverse group of proteins, representing
about 20-30% of the proteomes of most organisms, serving a multitude of cellular
functions and more than 40% of drug targets. Knowledge of a membrane protein
structure enables us insight into its function and dynamics, and can be used for
further rational drug design. Owing to the intrinsic hydrophobicity, flexibility,
and instability of membrane proteins, solid-state NMR may offer an unique oppor-
tunity to study membrane protein structure, ligand binding, and activation at atomic
resolution in the native membrane environment on a wide ranging time scale. Over
the past several years, solid-state NMR has made tremendous progress, showing its
capability of determining membrane protein structure, ligand binding, and protein
dynamic conformation on a variety of time scales at atomic resolution. In this
chapter we will mainly discuss some recent achievements on membrane protein
structure determination, ligand conformation and binding, structure changes upon
activation, and structure of insoluble fibrous proteins investigated by using magic-
angle spinning solid-state NMR from the structural biology point of view. Protein
dynamics, sensitivity enhancement, and the possibility of chemical shift-based
structure determination in solid-state NMR are also briefly touched upon.
Keywords Membrane proteins
MAS solid-state NMR
Structure determination
ligand conformation
structural changes and dynamics
