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Researchers Solve Structure of Protein Required for Cardiac Development
A research team at The University of Texas Medical School at Houston is the first to describe the three-dimensional structure for a family of proteins that are important to normal muscle and heart development.
Understanding the relationships between structure and function on the molecular level may someday lead to new ways to combat muscle degeneration, as in muscular dystrophy, and to find treatments for certain heart conditions.
Sudha Veeraraghavan, Ph.D., assistant professor of biochemistry in the Medical School and Graduate School of Biomedical Sciences, described the work in the Nov. 14 issue of the Proceedings of the National Academy of Sciences. The article described the structure for a family of proteins known as transcription enhancer factors (TEFs).
"For about 20 years, the structure and structural mechanism of their functions have remained a mystery," Veeraraghavan explained.
Pierre Chambon, M.D., one of the world's foremost experts in gene regulation, and his collaborator, Irwin Davidson, Ph.D., praised the research. "This new work represents an important advance in understanding the function of TEFs," they said.
"The TEF/TEAD family of factors are clearly important in regulating gene expression in many developmental systems," said Chambon and Davidson. Chambon is founder of the Institute for Genetics and Cellular and Molecular Biology in Strasbourg, France, where Davidson is a member of the institute's scientific committee and a team leader in the Transcription Department.
Alexandre Stewart, Ph.D., who has made significant contributions to the understanding of cardiac and skeletal muscle biology, said, "What makes this an exciting discovery is that through structure, we can better understand function. "
"This will permit the further characterization of the transcription factors that control gene expression in cardiac, skeletal and vascular smooth muscle, that control gene expression in vascular endothelium in response to hypoxia [a condition that occurs with coronary artery disease], that regulate fibrosis in the lungs, that control gene expression in the placenta, and that are required for the onset of zygotic [fertilized egg cell] development. Clearly, this discovery has far-reaching implications," said Stewart, who is assistant professor of medicine at the University of Ottawa Heart Institute.
In addition to being essential for normal development, this TEF family of proteins appears to be related to muscular dystrophy through one of its protein co-factors, Veeraraghavan said.
"Findings on TEFs and their co-factors also have potentially important implications to stem cell studies," she added. "When we have learned even more about the interplay between different transcription factors and TEFs, we could have suitable interventions for certain developmental disorders."
The results reported in the PNAS paper are predominantly the work of postdoctoral fellow Asokan Anbanandam, Ph.D., and research assistant, Diana Albarado. Collaborators included Xiaolian Gao, Ph.D., of the University of Houston, and George Halder, Ph.D., of the UT M. D. Anderson Cancer Center.
By Darla Brown, Medical School
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