Antiparallel
beta-sheet structure of the enzyme catalase: The antiparallel hydrogen bonds
(dotted) are
between peptide NH and CO groups on adjacent strands. Arrows indicate
the chain
direction, and electron density contours outline the non-H atoms.
Image: Wikimedia
Commons (edited by MIT News)
Enhanced-sensitivity NMR could reveal new clues to how
proteins fold.
(October 9, 2015) Proteins
can fold in different ways depending on their environment. These different
configurations change the function of the protein; misfolding is frequently
associated with diseases such as Alzheimer’s and Parkinson’s.
Until now, it has been difficult to fully characterize the
different structures that proteins can take on in their natural environments.
However, using a new technique known as sensitivity-enhanced nuclear magnetic
resonance (NMR), MIT researchers have shown that they can analyze the structure
that a yeast protein forms as it interacts with other proteins in a cell.
Using this type of NMR, which is based on a technique known
as dynamic nuclear polarization (DNP), scientists can gain much more insight
into protein structure and function than is possible with current NMR
technology, which requires large quantities of purified proteins, isolated from
their usual environment.
“Dynamic nuclear polarization has a capacity to transform
our understanding of biological structures in their native contexts,” says
Susan Lindquist, a professor of biology at MIT, member of the Whitehead
Institute, and one of the senior authors of the paper, which appears in the
Oct. 8 issue of Cell.
MIT researchers
used this gyrotron to generate the microwaves used to transfer polarization
from unpaired
electrons to protons. This allowed them to increase the sensitivity
of nuclear
magnetic resonance enough to study protein structures in their natural
environment.
Photo: Ta-Chung
Ong
Robert Griffin, an MIT professor of chemistry and director
of the Francis Bitter Magnet Laboratory, is also a senior author of the paper.
Kendra Frederick, a former Whitehead postdoc who is now an assistant professor
at the University of Texas Southwestern, is the paper’s lead author.
DNP-enhanced
sensitivity
Traditional NMR uses the magnetic properties of atomic
nuclei to reveal the structures of the molecules containing those nuclei. By
using a strong magnetic field that interacts with the nuclear spins of carbon
atoms in the proteins, NMR measures a trait known as chemical shift for some of
the individual atoms in the sample, which can reveal how those atoms are
connected.
“You look at changes in chemical shift and that tells you,
for example, if there is an alpha helix or a beta sheet, which are two
different conformations that a protein backbone often takes,” Frederick says.