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
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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