Fast-forward on P-type ATPases: recent advances on structure and function

Stock, Charlott; Heger, Tomáš; Hansen, Sara Basse; Larsen, Sigrid Thirup; Habeck, Michael; Dieudonné, Thibaud; Driller, Ronja; Nissen, Poul

doi:10.1042/bst20221543

Cited by 8 publications

(2 citation statements)

References 105 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NKA is classified as a member of the superfamily of P-type ATPases, which transport various compounds vectorially, ranging from H + to phospholipids, at the expense of ATP [ 60 ]. Due to its structural and functional characteristics, NKA is categorized as a type IIC-ATPase, sharing close relatives, such as H+/K + -ATPase and the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) [ 61 , 62 , 63 , 64 ]. Molecular characterization has revealed that each NKA functional unit comprises two or three subunits: α, β, and γ or FXYD.…”

Section: Nka’s Role As An Electrogenic Pumpmentioning

confidence: 99%

Na+/K+-ATPase: More than an Electrogenic Pump

Contreras,

Torres-Carrillo,

Flores-Maldonado

et al. 2024

IJMS

View full text Add to dashboard Cite

The sodium pump, or Na+/K+-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na+) and potassium (K+) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA’s role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell–cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA β-subunits as cell adhesion molecules in glia and epithelial cells.

show abstract

Section: Nka’s Role As An Electrogenic Pumpmentioning

confidence: 99%

Na+/K+-ATPase: More than an Electrogenic Pump

Contreras,

Torres-Carrillo,

Flores-Maldonado

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…K + homeostasis is central to enabling microbial survival under changing conditions. In many prokaryotes, high-affinity K + uptake at low extracellular K + concentrations is facilitated by the active K + pump KdpFABC 1 – 3 . Its chimeric composition of a K + channel and a P-type ATPase allows the complex to accumulate K + with an apparent affinity of 2 µM 4 .…”

Section: Introductionmentioning

confidence: 99%

KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally

Silberberg,

Ketter,

Böhm

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Two-component systems, consisting of a histidine kinase and a response regulator, serve signal transduction in bacteria, often regulating transcription in response to environmental stimuli. Here, we identify a tandem serine histidine kinase function for KdpD, previously described as a histidine kinase of the KdpDE two-component system, which controls production of the potassium pump KdpFABC. We show that KdpD additionally mediates an inhibitory serine phosphorylation of KdpFABC at high potassium levels, using not its C-terminal histidine kinase domain but an N-terminal atypical serine kinase domain. Sequence analysis of KdpDs from different species highlights that some KdpDs are much shorter than others. We show that, while Escherichia coli KdpD’s atypical serine kinase domain responds directly to potassium levels, a shorter version from Deinococcus geothermalis is controlled by second messenger cyclic di-AMP. Our findings add to the growing functional diversity of sensor kinases while simultaneously expanding the framework for regulatory mechanisms in bacterial potassium homeostasis.

show abstract

Structural Basis of Ion Transport in Copper‐Transporting P _IB ‐Type ATPases

Bågenholm,

Gourdon

2024

Encyclopedia of Inorganic and Bioinorganic Chemistry

View full text Add to dashboard Cite

Maintaining correct copper levels is vital for all cells, as copper is required for a large number of cellular processes, but is also toxic due to its high reactivity. Such regulation is accomplished using a range of processes, including the P IB‐1 ‐subgroup of P‐type ATPases. These primary active transporters exploit ATP to shuttle copper across cellular membranes, either out of the cell or into various organelles for cellular use, such as incorporation into copper‐dependent proteins. The pumping of copper across the membrane follows a conserved scheme, called the Post‐Albers cycle, where the protein cycles through a series of states, from inward‐open (E1) to inward‐occluded (E1P), outward‐open (E2P), and outward‐occluded (E2) and back, coupled to phosphorylation by ATP and dephosphorylation. This is established via a conserved core consisting of three soluble A‐, P‐, and N‐domains, and a transmembrane domain formed by eight membrane‐spanning helices, MA, MB, and M1–M6, as well as a varying number of metal‐binding domains MBDs, which typically are part of the N‐terminus. Copper is delivered to the P IB‐1 ‐transporter from small molecule or protein copper chaperones inside the cytoplasm, likely assisted by an MBD. The metal is then transferred to a methionine of M1 at the membrane interface, which relocates it to two conserved cysteines of the CPC motif in M4. Next, one or two high‐affinity‐binding sites are established in the M‐domain, again utilizing cysteines and methionines. Finally, release is achieved via an outward‐facing exit tunnel lined by methionines. While much of this pathway has been elucidated through determined molecular structures, important questions remain, for example, regarding the number of high‐affinity‐binding sites and the roles of the MBDs. Here, the structural details of the transport of copper through P IB‐1 ‐type ATPases will be described.

show abstract

Fast-forward on P-type ATPases: recent advances on structure and function

Cited by 8 publications

References 105 publications

Na+/K+-ATPase: More than an Electrogenic Pump

Na+/K+-ATPase: More than an Electrogenic Pump

KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally

Structural Basis of Ion Transport in Copper‐Transporting P _IB ‐Type ATPases

Contact Info

Product

Resources

About

Fast-forward on P-type ATPases: recent advances on structure and function

Cited by 8 publications

References 105 publications

Na+/K+-ATPase: More than an Electrogenic Pump

Na+/K+-ATPase: More than an Electrogenic Pump

KdpD is a tandem serine histidine kinase that controls K+ pump KdpFABC transcriptionally and post-translationally

Structural Basis of Ion Transport in Copper‐Transporting P IB ‐Type ATPases

Contact Info

Product

Resources

About

Structural Basis of Ion Transport in Copper‐Transporting P _IB ‐Type ATPases