New images of a
calcium-shuttling molecule that has been linked to aggressive cancer
Scientists have captured new images of a calcium-shuttling
molecule that has been linked to aggressive cancers. The three-dimensional
structure could help researchers develop novel therapies and diagnostic tools
for diseases that are caused by a malfunction in calcium adsorption.
Alexander Sobolevsky's lab at Columbia
University Medical Center is studying a family of proteins called
"Transient receptor potential (TRP)" channels. These proteins
line surfaces inside the body, such as the intestine, and form
pores that help calcium cross a dense
barrier of lipid and protein called the membrane to reach the interior of the
cell.
"Scientists have found that a TRP
channel variant, called TRPV6, is present in excess amounts in the tumor cells
of some cancer patients," says senior author Alexander Sobolevsky, PhD,
who is an assistant professor in the Department of Biochemistry and Molecular
Biophysics at Columbia University Medical Center. "And patients who
have higher quantities of TRPV6 seem to have a more aggressive form
of the disease."
In order to uncover how these channels guide
calcium into the cell, and how disease can occur when this process becomes
unregulated, Sobolevsky's lab used a technique called X-ray crystallography.
This process involved growing crystals of TRPV6 and exposing them to an X-ray
beam. The scientists then used the diffraction pattern produced by the X-rays
to map out a 3D model of the protein.
The structure—which represents a single
frozen state of the channel—reveals that the surface of TRPV6 pore is lined
with negative charges. This configuration helps attract calcium ions,
which are positively charged. The calcium ions are then shuffled from location
to location inside of the pore, up to three molecules at a time, as they
pass through into the cell.
"In future, we could use this model to
design drugs that can target some types of tumor cells by
plugging up TRP channels on their surfaces," says Sobolevsky.
Ordinarily the calcium ingested from our diet
is used by the body to regulate a variety of processes including the beating of
the heart, muscle contractions, and brain signaling. In addition to various
forms of cancer, altered calcium uptake and
TRPV6 expression has also been linked to Crohn's and kidney stone diseases in
mouse models. Further research needs to be done to determine the extent that
alteration in TRP channel activity leads to disease progression.
The structure of TRPV6 was published in a
recent issue of Nature.
No comments:
Post a Comment
Note: only a member of this blog may post a comment.