Decoding human biology one protein at a time
The human genome was sequenced many years ago and our ~20.000 genes are mostly defined. However, a large portion of our proteins, the products encoded by the genes and involved in all biological processes, remain functionally unexplored. University of Bergen researchers recently solved the structure and function of another uncharacterized human protein that turns out be linked to kidney disease.
Published: (Updated: )
One of the main challenges in understanding human biology is our lack of knowledge of the biochemical function of the proteins encoded by our genes. Despite knowing the sequence of all human genes and thus knowing the amino acid sequence of the proteins encoded by these genes, it is not possible to firmly predict protein function. Getting to this often involves careful work focusing on single proteins or small groups of proteins. The Arnesen lab at the Department of Biomedicine has been a part of this scientific effort for many years. Specifically, this lab has uncovered and defined a number of human proteins called acetyltransferases (external link). These proteins are enzymes catalyzing the transfer of a small chemical group, acetyl, from the metabolite Acetyl Coenzyme A to other proteins, amino acids or biomolecules. Earlier work established roles for these enzymes in cell motility (external link) and survival (external link), with physiological implications for cancer (external link), brain calcification (external link), cardiac disease (external link) and longevity (external link).
In their most recent work, researcher PhD Matti Myllykoski, PhD student Malin Lundekvam, senior engineer PhD Camilla Osberg and previous MSc student Solveig Siqveland Nilsen solved the crystal structure of the protein encoded by the NAT16 gene and defined its biochemical function to acetylate the amino acid Histidine. The NAT16 protein was therefore named Histidine acetyltransferase (HisAT). HisAT operates within human cells to acetylate Histidine and this acetylHistidine (AcHis) is then secreted into the blood where it may function as a signaling or buffer molecule. A NAT16 gene variant present in over 5% of the population was previously found to correlate with reduced plasma levels of AcHis and increased risk of kidney disease. Our biochemical analysis of this NAT16/HisAT protein variant shows reduced affinity for Histidine supporting a model where individuals expressing this variant generate AcHis more slowly leading to lower blood level of AcHis potentially impacting kidney function.
The published original article can be found here: The molecular basis for acetylhistidine synthesis by HisAT/NAT16 | Nature Communications (external link)
Structure of the NAT16/HisAT enzyme which catalyzes production of acetylhistidine by transferring acetyl from acetyl coenzyme A to histidine.
Related persons
Matti Aukusti Myllykoski (external link)
Researcher
The Department of Biomedicine (external link)
Matti.Myllykoski@uib.no
Malin Lundekvam (external link)
PhD Candidate
The Department of Biomedicine (external link)
Malin.Lundekvam@uib.no
Camilla Osberg (external link)
Senior Engineer
The Department of Biomedicine (external link)
Camilla.Osberg@uib.no
Thomas Arnesen (external link)
Professor, Group leader
The Department of Biomedicine (external link)
thomas.arnesen@uib.no