Biology, structure and mechanism of P-type ATPases

Kühlbrandt, Werner

doi:10.1038/nrm1354

Cited by 523 publications

(490 citation statements)

References 99 publications

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“…The proton pumping H þ -ATPase, Pma1, belongs to the P-type of cation transporting ATPases, which includes the Na þ /K þ -ATPase and Ca 2þ -ATPase of the mammalian plasma membrane [1]. A characteristic feature of P-type ATPases is that a strictly conserved aspartate residue is phosphorylated during the reaction cycle.…”

Section: Biogenesis and Transport Of The Proton Pumping H D -Atpasementioning

confidence: 99%

Lipid-dependent surface transport of the proton pumping ATPase: A model to study plasma membrane biogenesis in yeast

Toulmay

Schneiter

2007

Biochimie

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The proton pumping H þ -ATPase, Pma1, is one of the most abundant integral membrane proteins of the yeast plasma membrane. Pma1 activity controls the intracellular pH and maintains the electrochemical gradient across the plasma membrane, two essential cellular functions. The maintenance of the proton gradient, on the other hand, also requires a specialized lipid composition of this membrane. The plasma membrane of eukaryotic cells is typically rich in sphingolipids and sterols. These two lipids condense to form less fluid membrane microdomains or lipid rafts. The yeast sphingolipid is peculiar in that it invariably contains a saturated very long-chain fatty acid with 26 carbon atoms. During cell growth and plasma membrane expansion, both C26-containing sphingolipids and Pma1 are first synthesized in the endoplasmatic reticulum from where they are transported by the secretory pathway to the cell surface. Remarkably, shortening the C26 fatty acid to a C22 fatty acid by mutations in the fatty acid elongation complex impairs raft association of newly synthesized Pma1 and induces rapid degradation of the ATPase by rerouting the enzyme from the plasma membrane to the vacuole, the fungal equivalent of the lysosome. Here, we review the role of lipids in mediating raft association and stable surface transport of the newly synthesized ATPase, and discuss a model, in which the newly synthesized ATPase assembles into a membrane environment that is enriched in C26-containing lipids already in the endoplasmatic reticulum. The resulting proteinelipid complex is then transported and sorted as an entity to the plasma membrane. Failure to successfully assemble this lipideprotein complex results in mistargeting of the protein to the vacuole.

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Section: Biogenesis and Transport Of The Proton Pumping H D -Atpasementioning

confidence: 99%

Lipid-dependent surface transport of the proton pumping ATPase: A model to study plasma membrane biogenesis in yeast

Toulmay

Schneiter

2007

Biochimie

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“…All P-type ATPase proteins share a common structural core of intracellular A-(actuator), P-(phosphorylation), and N-(nucleotide binding) cytosolic domains and a transmembrane (TM) domain (17) (Fig. 1 A) (18,19) (Fig.…”

Section: Introductionmentioning

confidence: 99%

Membrane Anchoring and Ion-Entry Dynamics in P-type ATPase Copper Transport

Grønberg

Sitsel

Lindahl

et al. 2016

Biophysical Journal

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Cu þ -specific P-type ATPase membrane protein transporters regulate cellular copper levels. The lack of crystal structures in Cu þ -binding states has limited our understanding of how ion entry and binding are achieved. Here, we characterize the molecular basis of Cu þ entry using molecular-dynamics simulations, structural modeling, and in vitro and in vivo functional assays. Protein structural rearrangements resulting in the exposure of positive charges to bulk solvent rather than to lipid phosphates indicate a direct molecular role of the putative docking platform in Cu þ delivery. Mutational analyses and simulations in the presence and absence of Cu þ predict that the ion-entry path involves two ion-binding sites: one transient Met148-Cys382 site and one intramembranous site formed by trigonal coordination to Cys384, Asn689, and Met717. The results reconcile earlier biochemical and x-ray absorption data and provide a molecular understanding of ion entry in Cu þ -transporting P-type ATPases.

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“…These copper-binding sites are surface-exposed and thus accessible for copper binding. To enable copper translocation across the membrane, P-type ATPases have a metal binding site (M-domain) in the transmembrane helices [25]. Copper coordination in the M-domain is essential for ATPasedependent copper transport, and therefore three transmembrane helices contain invariant residues that coordinate copper in the M-domain (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…1); the Cys-Pro-Cys (CPC) motif in helix 6 [24], the Asp-Tyr (YN) motif in helix 7, and the Met-Xaa-Xaa-Ser (MxxS) motif in helix 8 coordinate copper in the M-domain [26][27][28]. Copper export by ATP7A and ATP7B is essentially dependent on the cyclic ATP hydrolysis activity [25]. ATP7A and ATP7B have several conserved motifs that are essential for their ATPase activity.…”

Section: Introductionmentioning

confidence: 99%