Cu(I)-Transport ATPases. Molecular Architecture, Catalysis and Adaptation to Extreme Environments

ALVARO RECOULAT ANGELINI; AGUEDA PLACENTI; NOELIA MELIAN; LURDES SABECKIS; NOELIA BURGARDT; RODOLFO M. GONZALEZ LEBRERO; ERNESTO A. ROMAN; FRANCISCO LUIS GONZALEZ FLECHA

Advances in Medicine and Biology

Nova

Año: 2021; p. 65 - 130

P-type ATPases constitutes a large group of integral membrane proteinsinvolved in the active transport across the cell membrane coupled to thehydrolysis of ATP. Among them, the Cu(I)-ATPases are present in cells from all three domains of life where, with the help of soluble chaperones, maintain intracellular copper(I) homeostasis. They share structural and functional features with all P-ATPases, including the formation of phosphorylated intermediates during the reaction cycle. In this chapter, we will analyze the structure, stability, adaptation to extreme environments and the catalytic mechanism of these α-helical membrane proteins. We review recent advances, regarding experimental work and hybrid QM/MM molecular dynamics simulations. Also, we present toy-model simulations that aid in the understanding of the ATP hydrolysis and transport coupling mechanisms.