Protein structure discovery could lead to better treatments for HIV, early aging

Apr 09, 2013 by Josh Barney

(Phys.org) —Researchers at the University of Virginia School of Medicine have determined the molecular structure of a protein whose mutations have been linked to several early aging diseases, and to side effects of common HIV and AIDS medications. This breakthrough could eventually help researchers develop new treatments for these early aging diseases and redesign AIDS medications to avoid side effects, such as diabetes.

U.Va. Center for Membrane Biology researchers Peter S. Horanyi, Edward E. Pryor Jr., and Michael C. Wiener collaborated with groups from the Hauptman-Woodward Medical Research Institute and the University of Rochester School of Medicine and Dentistry to determine the molecular structure of the enzyme Ste24p. Their findings were published March 29 in the journal Science.

Their Membrane Protein Consortium is funded by the National Institutes of Health's Protein Structure Initiative, which supports the determination of molecular structures of biomedically important .

The nucleus of a cell is lined with a mesh-like structure called lamin that serves as a scaffold for maintaining and function. Lamin requires the action of another protein, called Ste24p protease, which removes specific parts of the lamin filament and enables proper assembly of the mesh.

The research team determined the structure of a Ste24p protein found in a close relative of baker's yeast, whose properties are interchangeable with the same protein found in humans.
The experiments required to solve the of Ste24p were performed remotely at the Advanced Photon Source, part of the Department of Energy's Argonne National Laboratory near Chicago.

U.Va. funds access to the laboratory, Horanyi said, to enable researchers to use specialized X-ray crystallographic capabilities available through the South East Regional Collaborative Access Team at the . Working from Charlottesville, U.Va. researchers can log onto a computer program to remotely control the robots to perform research and to collect data. "It's like using a Web application," Horanyi said.

In humans, improper processing and assembly of lamin leads to a group of diseases known as laminopathies, which include muscular dystrophy, cardiomyopathies and a collection of rare accelerated aging diseases in children called progerias. The research team focused on Ste24p, Pryor said, because defects in this protein in humans are responsible for a number of progerias. In addition, some frequently used HIV and AIDS medications utilized in Highly Active Antiretroviral Therapy, or HAART, also interact with Ste24p, altering how patients taking the drugs metabolize fat and leading to treatment that can include insulin resistance and diabetes, Pryor said.

Knowing how the protein is structured could aid researchers in developing drugs to treat progerias and could assist in the redesign of HAART medications to avoid the treatment side effects, Wiener said.

Pryor noted that Ste24p is a biomarker for normal aging in humans – as humans get older, this works less effectively. "So this mapping could provide insight to researchers into the aging process for humans," he said.

Explore further: Researchers successfully clone adult human stem cells

add to favorites email to friend print save as pdf

Related Stories

A fly lamin gene is both like and unlike human genes

Jun 13, 2007

Mitch Dushay and colleagues at Uppsala University in Sweden announce the publication of their paper, "Characterization of lamin Mutation Phenotypes in Drosophila and Comparison to Human Laminopathies" in the June 13th issue ...

Scientists describe mechanism for rare muscle disease

Oct 03, 2011

(Medical Xpress) -- A team of scientists from the Friedrich Miescher Institute for Biomedical Research and the Hebrew University of Jerusalem describe in C. elegans the process leading to a rare form of Emery-Dreifuss ...

Clues point to cause of a rare fat-distribution disease

Mar 20, 2013

Studying a protein that gives structure to the nucleus of cells, Johns Hopkins researchers stumbled upon mutations associated with familial partial lipodystrophy (FPLD), a rare disease that disrupts normal patterns of fat ...

Lamin B locks up Oct-1

Jan 12, 2009

A large fraction of the transcription factor Oct-1 is associated with the inner nuclear envelope, but how and why it is retained there was unknown.

Recommended for you

Researchers successfully clone adult human stem cells

19 hours ago

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Researchers develop new model of cellular movement

22 hours ago

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

For resetting circadian rhythms, neural cooperation is key

Apr 17, 2014

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

User comments : 0

More news stories

Researchers successfully clone adult human stem cells

(Phys.org) —An international team of researchers, led by Robert Lanza, of Advanced Cell Technology, has announced that they have performed the first successful cloning of adult human skin cells into stem ...

Male monkey filmed caring for dying mate (w/ Video)

(Phys.org) —The incident was captured by Dr Bruna Bezerra and colleagues in the Atlantic Forest in the Northeast of Brazil.  Dr Bezerra is a Research Associate at the University of Bristol and a Professor ...

Researchers develop new model of cellular movement

(Phys.org) —Cell movement plays an important role in a host of biological functions from embryonic development to repairing wounded tissue. It also enables cancer cells to break free from their sites of ...

Health care site flagged in Heartbleed review

People with accounts on the enrollment website for President Barack Obama's signature health care law are being told to change their passwords following an administration-wide review of the government's vulnerability to the ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.