The binding of polyamines to phospholipid bilayers

Yung, M. W.; Green, Colin

doi:10.1016/0006-2952(86)90024-9

Cited by 37 publications

(4 citation statements)

References 20 publications

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“…Lipids may play an important structural and functional role in membrane proteins as suggested by the crystal and cryo-EM structures in which the densities of sparse lipids have been occasionally captured 40 , 41 . Accordingly, a belt of substantial densities near the substrate release site was clearly captured in our EM maps and further identified as PIP2 or POPA by our coarse-grained MD simulations, consistent with previous and recent reports 22 , 42 . This finding implies that these phospholipids actively regulate hATP13A2 transport.…”

Section: Discussionsupporting

confidence: 91%

Conformational cycle of human polyamine transporter ATP13A2

Xue

et al. 2023

Nat Commun

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Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson’s disease and autosomal recessive spastic paraplegia 78, is a transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases. These structures comprise a nearly complete conformational cycle spanning the polyamine transport process and capture multiple substrate binding sites distributed along the transmembrane regions, suggesting a potential polyamine transport pathway. Integration of high-resolution structures, biochemical assays, and molecular dynamics simulations allows us to obtain a better understanding of the structural basis of how hATP13A2 transports polyamines, providing a mechanistic framework for ATP13A2-related diseases.

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Section: Discussionsupporting

confidence: 91%

Conformational cycle of human polyamine transporter ATP13A2

Xue

et al. 2023

Nat Commun

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“…It should be noted that an ionic interaction between polyamines and phospholipids vesicles has been reported (Yung and Green, 1986). Indeed, high concentrations (mM) of spermine have been used to screen PIP 2 and inhibit K ATP channels (Fan and Makielski, 1997).…”

Section: Discussionmentioning

confidence: 98%

Long Polyamines Act as Cofactors in PIP2 Activation of Inward Rectifier Potassium (Kir2.1) Channels

Xie

John

Ribalet

et al. 2005

The Journal of General Physiology

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Phosphatidylinosital-4,5-bisphosphate (PIP2) acts as an essential factor regulating the activity of all Kir channels. In most Kir members, the dependence on PIP2 is modulated by other factors, such as protein kinases (in Kir1), Gβγ (in Kir3), and the sulfonylurea receptor (in Kir6). So far, however, no regulator has been identified in Kir2 channels. Here we show that polyamines, which cause inward rectification by selectively blocking outward current, also regulate the interaction of PIP2 with Kir2.1 channels to maintain channel availability. Using spermine and diamines as polyamine analogs, we demonstrate that both spontaneous and PIP2 antibody–induced rundown of Kir2.1 channels in excised inside-out patches was markedly slowed by long polyamines; in contrast, polyamines with shorter chain length were ineffective. In K188Q mutant channels, which have a low PIP2 affinity, application PIP2 (10 μM) was unable to activate channel activity in the absence of polyamines, but markedly activated channels in the presence of long diamines. Using neomycin as a measure of PIP2 affinity, we found that long polyamines were capable of strengthening either the wild type or K188Q channels' interaction with PIP2. The negatively charged D172 residue inside the transmembrane pore region was critical for the shift of channel–PIP2 binding affinity by long polyamines. Sustained pore block by polyamines was neither sufficient nor necessary for this effect. We conclude that long polyamines serve a dual role as both blockers and coactivators (with PIP2) of Kir2.1 channels.

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“…Ionic interactions between polyamines and acidic phospholipids are strongest between the polyamine with the highest positive charges and the phospholipid with the highest content of negative groups (Yung and Green, 1986). Interaction with polyamines is believed to reduce the repulsive forces between negatively charged membrane components by bridging proteins and lipids and by shielding the surface charges (Schuber, 1989).…”

Section: Lipid Domainsmentioning

confidence: 99%

The membrane: transertion as an organizing principle in membrane heterogeneity

et al. 2015

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The bacterial membrane exhibits a significantly heterogeneous distribution of lipids and proteins. This heterogeneity results mainly from lipid–lipid, protein–protein, and lipid–protein associations which are orchestrated by the coupled transcription, translation and insertion of nascent proteins into and through membrane (transertion). Transertion is central not only to the individual assembly and disassembly of large physically linked groups of macromolecules (alias hyperstructures) but also to the interactions between these hyperstructures. We review here these interactions in the context of the processes in Bacillus subtilis and Escherichia coli of nutrient sensing, membrane synthesis, cytoskeletal dynamics, DNA replication, chromosome segregation, and cell division.

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The binding of polyamines to phospholipid bilayers

Cited by 37 publications

References 20 publications

Conformational cycle of human polyamine transporter ATP13A2

Conformational cycle of human polyamine transporter ATP13A2

Long Polyamines Act as Cofactors in PIP2 Activation of Inward Rectifier Potassium (Kir2.1) Channels

The membrane: transertion as an organizing principle in membrane heterogeneity

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