On Allosteric Modulation of P-Type Cu⁺-ATPases

TY - JOUR

T1 - On Allosteric Modulation of P-Type Cu+-ATPases

AU - Mattle, Daniel

AU - Sitsel, Oleg

AU - Autzen, Henriette Elisabeth

AU - Meloni, Gabriele

AU - Gourdon, Pontus

AU - Nissen, Poul

PY - 2013/7/10

Y1 - 2013/7/10

N2 - P-type ATPases perform active transport of various compounds across biological membranes and are crucial for ion homeostasis and the asymmetric composition of lipid bilayers. Although their functional cycle share principles of phosphoenzyme intermediates, P-type ATPases also show subclass-specific sequence motifs and structural elements that are linked to transport specificity and mechanistic modulation. Here we provide an overview of the Cu+-transporting ATPases (of subclass PIB) and compare them to the well-studied sarco(endo)plasmic reticulum Ca2 +-ATPase (of subclass PIIA). Cu+ ions in the cell are delivered by soluble chaperones to Cu+-ATPases, which expose a putative “docking platform” at the intracellular interface. Cu+-ATPases also contain heavy-metal binding domains providing a basis for allosteric control of pump activity. Database analysis of Cu+ ligating residues questions a two-site model of intramembranous Cu+ binding, and we suggest an alternative role for the proposed second site in copper translocation and proton exchange. The class-specific features demonstrate that topological diversity in P-type ATPases may tune a general energy coupling scheme to the translocation of compounds with remarkably different properties.

AB - P-type ATPases perform active transport of various compounds across biological membranes and are crucial for ion homeostasis and the asymmetric composition of lipid bilayers. Although their functional cycle share principles of phosphoenzyme intermediates, P-type ATPases also show subclass-specific sequence motifs and structural elements that are linked to transport specificity and mechanistic modulation. Here we provide an overview of the Cu+-transporting ATPases (of subclass PIB) and compare them to the well-studied sarco(endo)plasmic reticulum Ca2 +-ATPase (of subclass PIIA). Cu+ ions in the cell are delivered by soluble chaperones to Cu+-ATPases, which expose a putative “docking platform” at the intracellular interface. Cu+-ATPases also contain heavy-metal binding domains providing a basis for allosteric control of pump activity. Database analysis of Cu+ ligating residues questions a two-site model of intramembranous Cu+ binding, and we suggest an alternative role for the proposed second site in copper translocation and proton exchange. The class-specific features demonstrate that topological diversity in P-type ATPases may tune a general energy coupling scheme to the translocation of compounds with remarkably different properties.

U2 - 10.1016/j.jmb.2013.03.008

DO - 10.1016/j.jmb.2013.03.008

M3 - Review

C2 - 23500486

SN - 0022-2836

VL - 425

SP - 2299

EP - 2308

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 13

ER -