Paper published in Nature Communications Biology
The paper “An intact C-terminal end of albumin is required for its long half-life in humans” has just been published in Nature Communications Biology.
This work is the first paper from a fruitful collaboration between the Protein Analysis Group and the Lab of Adaptive Immunity and Homeostasis, Oslo University Hospital, headed by Jan Terje Andersen.
Albumin is the most abundant serum protein and has a remarkably long half-life in the human body of approximately 3 weeks. The long half-life is due to its pH-dependent interaction with the Neonatal Fc Receptor (FcRn). In the current study it is shown that deletion of the C-terminal residue in albumin (L585), a deletion observed in patients with acute pancreatitis, dramatically decreases the half-life of albumin. By comparing the hydrogen/deuterium exchange of wildtype albumin and the truncated form of albumin (L585X), Esben and Kasper could reveal that removal of the C-terminal residue causes a structural stabilization in the DIII domain. This structural stabilization causes a decrease in affinity towards FcRn. Hence, structural flexibility of DIII is important to secure a long half-life of albumin, a finding that has implications for design of albumin-based biopharmaceuticals.