Structure and Function of Cu(I)- and Zn(II)-ATPases

Sitsel, Oleg; Grønberg, Christina; Autzen, Henriette Elisabeth; Wang, Kaituo; Meloni, Gabriele; Nissen, Poul; Gourdon, Pontus

doi:10.1021/acs.biochem.5b00512

Cited by 47 publications

(49 citation statements)

References 117 publications

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“…KdpB is characterized by seven transmembrane helices, the first six of which are consistent with the 'core' of other P-type ATPases19. The middle of bM4 is unwound at the conserved proline motif (IP 264 TTI) and very similar to M4 of the Ca 2+ -ATPase (SERCA1a) in the Ca 2+ bound E1 state 10 (Extended Data Fig.…”

mentioning

confidence: 67%

Crystal structure of the potassium-importing KdpFABC membrane complex

Huang

Pedersen

Stokes

2017

Nature

101

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Cellular potassium import systems play a fundamental role in osmoregulation, pH homeostasis and membrane potential in all domains of life. In bacteria, the kdp operon encodes a four subunit potassium pump that maintains intracellular homeostasis as well as cell shape and turgor under conditions where potassium is limiting1. This membrane complex, called KdpFABC, has one channel-like subunit (KdpA) belonging to the Superfamily of Potassium Transporters and another pump-like subunit (KdpB) belonging to the Superfamily of P-type ATPases. Although there is considerable structural and functional information about members from both superfamilies, the mechanism by which uphill potassium transport through KdpA is coupled with ATP hydrolysis by KdpB remains poorly understood. Here we report the 2.9 Å X-ray structure of the complete Escherichia coli KdpFABC complex with a potassium ion within the selectivity filter of KdpA as well as a water molecule at a canonical cation site in the transmembrane domain of KdpB. The structure also reveals two structural elements that appear to mediate the coupling between these two subunits. Specifically, a protein-embedded tunnel runs between these potassium and water sites and a helix controlling the cytoplasmic gate of KdpA is linked to the phosphorylation domain of KdpB. Based on these observations, we propose an unprecedented mechanism that repurposes protein channel architecture for active transport across biomembranes.

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confidence: 67%

Crystal structure of the potassium-importing KdpFABC membrane complex

Huang

Pedersen

Stokes

2017

Nature

101

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“…P‐1B‐2 ATPase enzymes contain the Cys‐Pro‐Cys motif in the center of the sixth transmembrane domain (TMD), Lys in seventh TMD and Asp and Gly in the eighth TMD, as a putative component of the corresponding transmembrane metal binding site . The studies on ZntA from Shigella sonnei show that two amino acid residues: Asp714 (situated close to the CPC motif) and Lys693 are necessary for the activity of ATPase …”

Section: Bacterial Zinc Homeostasismentioning

confidence: 55%

“…[83b, 84] The studies on ZntA from Shigella sonnei show that two amino acid residues: Asp714 (situated close to the CPC motif) and Lys693 are necessary for the activity of ATPase. [86] P1B-Zn II ATPase from E. coli has a~120 residue N-terminal domain with as ingle repeat of the GXXCXXC motif andf our additional cysteiner esidues (in the form of aC CCDXXC sequence). [81b] The conserved CXXC motif near the N-terminus in the cytoplasmic domain and CPC motif located in the transmembrane fragment are involved in binding of the translocated metal.…”

Section: Export Systemsmentioning

confidence: 99%

Zinc Homeostasis at the Bacteria/Host Interface—From Coordination Chemistry to Nutritional Immunity

Wątły

Potocki

Rowińska‐Żyrek

2016

Chemistry A European J

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Zinc is one of the most important metal nutrients for species from all kingdoms, being a key structural or catalytic component of hundreds of enzymes, crucial for the survival of both pathogenic microorganisms and their hosts. This work is an overview of the homeostasis of zinc in bacteria and humans. It explains the importance of this metal nutrient for pathogens, describes the roles of zinc sensors, regulators, and transporters, and summarizes various uptake systems and different proteins involved in zinc homeostasis-both those used for storage, buffering, and signaling inside the cell and those excreted in order to obtain Zn from the host. The human zinc-dependent immune system response is explained, with a special focus given to 'zinc nutritional immunity', a process that describes the competition between the bacteria or fungus and the host for this metal, during which both the pathogen and host make huge efforts to control zinc availability. This sophisticated tug of war over Zn might be considered as a possible target for novel antibacterial therapies.

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“…It is likely that other P-type ATPases for which their structural mechanisms are less known, such as the Zn 2+ - and Cu + -transporting ATPases, 77, 78 use a similar E2-E1 mechanism to couple structural changes with ion transport. 79 We propose that preexisting domain motions that underlie the E2-E1 structural transition described in this study are a common theme in ligand-induced structural shifts associated with function of the P-type ATPase superfamily.…”

Section: Discussionmentioning

confidence: 74%

Preexisting domain motions underlie protonation-dependent structural transitions of the P-type Ca²⁺-ATPase

Gortari

Espinoza-Fonseca

2017

Phys. Chem. Chem. Phys.

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We have performed microsecond molecular dynamics (MD) simulations to determine the mechanism for protonation-dependent structural transitions of the sarcoplasmic reticulum Ca2+-ATPase (SERCA). Release of two H+ from the transport sites activates SERCA by inducing a structural transition between low (E2) and high (E1) Ca2+-affinity states (E2-to-E1 transition), but the structural mechanism by which transport site deprotonation facilitates this transition is unknown. We performed microsecond all-atom MD simulations to determine the effects of transport site protonation on the structural dynamics of the E2 state in solution. We found that the protonated E2 state has structural characteristics that are similar to those observed in crystal structures of E2. Upon deprotonation, a single Na+ ion rapidly (<10 ns) binds to the transmembrane transport sites and induces a kink in M5, disrupts the M3–M5 interface, and increases the mobility of M3/A-M3 linker. Principal component analysis showed that counter-rotation of the cytosolic N-A domains about the membrane normal axis, which is the primary motion driving the E2-to-E1 transition, is present in both protonated and deprotonated E2 states; however, protonation-dependent structural changes in the transmembrane domain control the hierarchical organization and amplitude of this motion. We propose that preexisting rigid-body domain motions underlie structural transitions of SERCA, where the functionally important directionality is preserved while transport site protonation controls the dominance and amplitude of motion to shift the equilibrium between the E1 and E2 states. We conclude that ligand-induced modulation of preexisting domain motions is likely a common theme in structural transitions of the P-type ATPase superfamily.

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Structure and Function of Cu(I)- and Zn(II)-ATPases

Cited by 47 publications

References 117 publications

Crystal structure of the potassium-importing KdpFABC membrane complex

Crystal structure of the potassium-importing KdpFABC membrane complex

Zinc Homeostasis at the Bacteria/Host Interface—From Coordination Chemistry to Nutritional Immunity

Preexisting domain motions underlie protonation-dependent structural transitions of the P-type Ca²⁺-ATPase

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Structure and Function of Cu(I)- and Zn(II)-ATPases

Cited by 47 publications

References 117 publications

Crystal structure of the potassium-importing KdpFABC membrane complex

Crystal structure of the potassium-importing KdpFABC membrane complex

Zinc Homeostasis at the Bacteria/Host Interface—From Coordination Chemistry to Nutritional Immunity

Preexisting domain motions underlie protonation-dependent structural transitions of the P-type Ca2+-ATPase

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Preexisting domain motions underlie protonation-dependent structural transitions of the P-type Ca²⁺-ATPase