An intact C-terminal end of albumin is required for its long half-life in humans
Autor: | Malin C. Bern, Inger Sandlie, Kasper D. Rand, Cláudia Azevedo, Algirdas Grevys, Jan Terje Andersen, Jeannette Nilsen, Bjørn Dalhus, John J Wilson, Maria Stensland, Derry C. Roopenian, Stephen O. Brennan, Kine Marita Knudsen Sand, Esben Trabjerg |
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Přispěvatelé: | Instituto de Investigação e Inovação em Saúde |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
Carboxypeptidases A Medicine (miscellaneous) Receptors Fc Carboxypeptidases A / blood Serum Albumin Human / genetics Histocompatibility Antigens Class I / genetics lcsh:QH301-705.5 Receptors Fc / genetics 0303 health sciences Protein Stability Chemistry Recombinant Proteins / metabolism 030302 biochemistry & molecular biology Serum Albumin Human / metabolism Half-life Cellular receptor Recombinant Proteins Amylases Pancreatitis / blood Structural biology General Agricultural and Biological Sciences Pancreas / enzymology Intracellular Half-Life Protein Binding Binding domain Pancreatitis / enzymology Mice Transgenic Serum Albumin Human Article General Biochemistry Genetics and Molecular Biology Histocompatibility Antigens Class I / metabolism Structure-Activity Relationship 03 medical and health sciences Residue (chemistry) Protein Domains Pharmacokinetics Animals Humans Pancreas Recombinant Proteins / chemistry 030304 developmental biology Receptors Fc / metabolism Molecular engineering Histocompatibility Antigens Class I Albumin Proteins Lipase Serum Albumin Human / chemistry Lipase / blood Pancreatitis lcsh:Biology (General) Amylases / blood Proteolysis Biophysics Post-translational modifications |
Zdroj: | Communications Biology, Vol 3, Iss 1, Pp 1-11 (2020) Nilsen, J, Trabjerg, E, Grevys, A, Azevedo, C, Brennan, S O, Stensland, M, Wilson, J, Sand, K M K, Bern, M, Dalhus, B, Roopenian, D C, Sandlie, I, Rand, K D & Andersen, J T 2020, ' An intact C-terminal end of albumin is required for its long half-life in humans ', Communications Biology, vol. 3, no. 1, 181 . https://doi.org/10.1038/s42003-020-0903-7 Communications Biology, 3 (1) Communications Biology |
ISSN: | 2399-3642 |
Popis: | Albumin has an average plasma half-life of three weeks and is thus an attractive carrier to improve the pharmacokinetics of fused therapeutics. The half-life is regulated by FcRn, a cellular receptor that protects against intracellular degradation. To tailor-design the therapeutic use of albumin, it is crucial to understand how structural alterations in albumin affect FcRn binding and transport properties. In the blood, the last C-terminal residue (L585) of albumin may be enzymatically cleaved. Here we demonstrate that removal of the L585 residue causes structural stabilization in regions of the principal FcRn binding domain and reduces receptor binding. In line with this, a short half-life of only 3.5 days was measured for cleaved albumin lacking L585 in a patient with acute pancreatitis. Thus, we reveal the structural requirement of an intact C-terminal end of albumin for a long plasma half-life, which has implications for design of albumin-based therapeutics. Communications Biology, 3 (1) ISSN:2399-3642 |
Databáze: | OpenAIRE |
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