The blue region is where the amino acids are bound. The centre of the binding of the acids is highlighted. The model was used to determine how different acids bind the transporter. Oscar Llorca is a person.
The HAT family of proteins are essential for life as they transport amino acids. Some members of the family are different from others. This specialization determines their involvement in specific functions, such as cell growth or neuronal functions, and consequently in related diseases like cancer or Alzheimer's disease. What makes up the diversity of functions? This is one of the questions asked by the researchers at the Spanish National Cancer Research Center and the Institute for Research in Biomedicine, who led the study, and one of the answers has been published in a journal.
Thanks to the latest high-resolution structural technologies, the researchers have been able to observe the structure of one of the members of the family in atomic detail and decipher its function. The results of the study show that only a few of the family's residues are located in defined regions, and that they are responsible for binding the specific amino acids to which they will bind.
With this information, the researchers now face the challenge of finding new therapies and diagnostic tools for diseases that involve the HAT family of transporters, with a particular interest in those conditions that pose serious health problems, such as cancer and Alzheimer's disease.
Understanding how to disrupt their function.
The basic building blocks of life are Amino acids. The movement into and out of the cell occurs thanks to the gates embedded in the cell's cell wall.
The transport of toxic substances and involvement in addiction are some of the functions that can be achieved by some HAT proteins.
Scientists are studying the 3D structure of this important family of proteins to understand the specificity of function. "Classical techniques used to determine the structure of proteins, such as those using X-rays, have had limited success with proteins that are embedded in biological membranes, and so many questions have remained unresolved," says Oscar Llorca, head of the Macromolecular Complexes in DNA Damage Response Group The head of the Amino Acid and Disease Transporters laboratory at IRB Barcelona, professor of the University of Barcelona and Unit leader of CI, says that they have applied this technology to identify the mechanisms that lead to the transport of some amino acids but not others.
New drugs for Alzheimer's disease.
The visualization of the structure of themolecular structure of the proteins has taken a giant step towards what we now know as the golden age of 3D structures thanks to Llorca. This new technology, which won the chemistry prize in the year of 2017, is helping to accelerate the development of new compounds and drugs of interest to treat cancer and other human diseases, as well as observing biological processes like never before.
The structure of a member of the HAT family at atomic resolution and the details of the mechanism by which this recognition occurs have been visualized by the researchers.
The atomic details show that only a small amount of the proteins's residues determine the function of their specific functions. The study shows how the substitution of some residues for others in these positions in the different members of the family can affect the specificity of recognition and transport of some amino acids.
The research results could lead to compounds that act on specific regions of the proteins, and to manage the disorders in which they participate, such as cancer and Alzheimer's disease.
There is more information about the basis for the specificity of the Heteromeric transporters. There is a DOI: 10.1073/pnas.2113573118.
The National Academy of Sciences has a journal.
The mode of action of essential proteins involved in cancer and Alzheimer's disease was determined by scientists.
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