Mutations in this molecule may have helped mammoths tolerate the cold

August 27, 2018, Columbia University Irving Medical Center
Mutations in this molecule may have helped mammoths tolerate the cold
Enhanced 2-D images of TRPV3 molecules at different orientations. Credit: Alexander Sobolevsky / CUIMC

Columbia University biomedical researchers have captured close-up views of TRPV3, a skin-cell ion channel that plays important roles in sensing temperature, itch, and pain. In humans, defects in the protein can lead to skin diseases such as atopic dermatitis (a type of eczema), vitiligo (uneven skin coloration), skin cancer, and rosacea.

All vertebrate DNA, including the woolly mammoth genome, contains the TRPV3 gene. Though the mammoths lived in extremely cold environments, they descended from elephants that lived in the tropics. Researchers think that changes in the TRPV3 genes of mammoths may have helped them withstand lower temperatures.

Alexander Sobolevsky's lab at Columbia University Irving Medical Center used a powerful imaging technique called cryo-electron microscopy to take pictures of TRPV3 molecules. Initial 2-D images were collected by freezing the molecules in an extremely thin, clear layer of ice and bombarding them with electrons. The researchers then used computational tools to convert the 2-D images into detailed molecular 3-D models.

Mutations in this molecule may have helped mammoths tolerate the cold
Human TRPV3 in the closed and open states viewed from outside the cell. Location of the region (N647) that is mutated in mammoths is highlighted. Credit: Alexander Sobolevsky / CUIMC

This is the first time scientists have gotten a glimpse of TRPV3 in atomic detail. The researchers were able to get images of the protein in two states, revealing how the channel opens and closes to let ions flow into skin cells. This exchange of ions prompts the body to react to sensations such as pain, itchiness, and changes in temperature. The group also discovered how a small molecule with anti-cancer properties called 2-APB interacts with and controls the function of this channel.

The structures in this study provide clues about how mutations in TRPV3 affect the channel's ability to sense temperature and show that lipids—molecules that make up most of the cell membrane—contact the channel in several regions. Mammoth TRPV3 contains a mutation in one of these lipid-touching regions. "Temperature affects the interaction of lipids and proteins," Sobolevsky says. "A mutation in the woolly mammoth channel would most likely affect this interaction and could explain how these animals adapted to their cold environment."

Researchers will use the structure to investigate how atomic changes to the protein cause it to malfunction in human diseases. "This study gives scientists a template they can use to design more effective drugs for treating these skin-related illnesses," said Appu Singh, Ph.D., a postdoctoral fellow in the Sobolevsky lab and a first author of the paper.

Alexander Sobolevsky, Ph.D., is an associate professor of biochemistry and molecular biophysics at Columbia University Vagelos College of Physicians and Surgeons.

Explore further: Researchers identify cellular basis for how anti-aging costmetics work

More information: Appu K. Singh, Luke L. McGoldrick, Alexander I. Sobolevsky. Structure and gating mechanism of the transient receptor potential channel TRPV3. Nature Structural & Molecular Biology, 2018; DOI: 10.1038/s41594-018-0108-7

Related Stories

Recommended for you

In colliding galaxies, a pipsqueak shines bright

February 20, 2019

In the nearby Whirlpool galaxy and its companion galaxy, M51b, two supermassive black holes heat up and devour surrounding material. These two monsters should be the most luminous X-ray sources in sight, but a new study using ...

Research reveals why the zebra got its stripes

February 20, 2019

Why do zebras have stripes? A study published in PLOS ONE today takes us another step closer to answering this puzzling question and to understanding how stripes actually work.

When does one of the central ideas in economics work?

February 20, 2019

The concept of equilibrium is one of the most central ideas in economics. It is one of the core assumptions in the vast majority of economic models, including models used by policymakers on issues ranging from monetary policy ...

Correlated nucleons may solve 35-year-old mystery

February 20, 2019

A careful re-analysis of data taken at the Department of Energy's Thomas Jefferson National Accelerator Facility has revealed a possible link between correlated protons and neutrons in the nucleus and a 35-year-old mystery. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.