Chemistry Reference
In-Depth Information
The Use of Residual Dipolar Coupling
in Studying Proteins by NMR
Kang Chen and Nico Tjandra
Abstract The development of residual dipolar coupling (RDC) in protein NMR
spectroscopy, over a decade ago, has become a useful and almost routine tool for
accurate protein solution structure determination. RDCs provide orientation infor-
mation of magnetic dipole-dipole interaction vectors within a common reference
frame. Its measurement requires a nonisotropic orientation, through a direct or
indirect magnetic field alignment, of the protein in solution. There has been recent
progress in the developments of alignment methods to allow the measurement of
RDC and of methods to analyze the resulting data. In this chapter we briefly go
through the mathematical expressions for the RDC and common descriptions of the
alignment tensor, which may be represented using either Saupe order or the
principal order matrix. Then we review the latest developments in alignment
media. In particular we looked at the lipid-compatible media that allow the mea-
surement of RDCs for membrane proteins. Other methods including conservative
surface residue mutation have been invented to obtain up to five orthogonal
alignment tensors that provide a potential for de novo structure and dynamics
study using RDCs exclusively. We then discuss approximations assumed in RDC
interpretations and different views on dynamics uncovered from the RDC method.
In addition to routine usage of RDCs in refining a single structure, novel
applications such as ensemble refinement against RDCs have been implemented
to represent protein structure and dynamics in solution. The RDC application also
extends to the study of protein-substrate interaction as well as to solving quaternary
structure of oligomer in equilibrium with a monomer, opening an avenue for RDCs
in high-order protein structure determination.
Keywords RDC
Alignment medium
Ensemble
Dynamics
Oligomer
