Energetics Of Peptide (pHLIP) Binding To And Folding Across A Lipid Bilayer Membrane

Reshetnyak, Yana K.; Andreev, Oleg A.; Segala, Michael; Markin, Vladislav S.; Engelman, Donald M.

doi:10.1016/j.bpj.2008.12.1836

Cited by 14 publications

(25 citation statements)

References 16 publications

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“…However, it is of note that the lipid to peptide ratio used in the NMR experiments was 75:1, whereas our simulations were conducted at a ratio of 200:1. Previous studies have shown that binding of pHLIP is affected by lower lipid:peptide ratios, leading to a "parking problem" for pHLIP on the bilayer surface (9). For the orientations that remained bound to POPC, the 0 • , 72 • , and 288 • orientations all had distance distributions for A27 that were > 10 Å in agreement with the NMR experiments.…”

Section: Partitioning Of Phlip Influenced By Location Of Acidic Residuessupporting

confidence: 79%

“…Peptide insertion is induced by a shift from alkaline to acidic pH, with an apparent pK of insertion in 1-palmitoyl-2-oleoyl-snglycero-3-phosphocholine (POPC) membranes of ∼6.1 (9). This shift in pH spurs the protonation of two acidic residues (D14 and D25) in the membrane-spanning region of the peptide, leading to an increase in hydrophobicity and triggering the folding and insertion of the peptide across the lipid bilayer (9,10). The presence of two tryptophan residues (W9 and W15) allow intrinsic fluorescence spectroscopy to be used to detect the transition of pHLIP from state I → II → III.…”

Section: Introductionmentioning

confidence: 99%

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Cooperative Non-bonded Forces Control Membrane Binding of the pH-Low Insertion Peptide pHLIP

Gupta

Ren

Mertz

2018

Preprint

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Peptides with the ability to bind and insert into the cell membrane have immense potential in biomedical applications. pH (Low) Insertion Peptide (pHLIP), a water-soluble polypeptide derived from helix C of bacteriorhodopsin, can insert into a membrane at acidic pH to form a stable transmembrane α-helix. The insertion process takes place in three stages: pHLIP is unstructured and soluble in water at neutral pH (state I), unstructured and bound to the surface of a membrane at neutral pH (state II), and inserted into the membrane as an α-helix at low pH (state III). Using molecular dynamics (MD) simulations, we have modeled state II of pHLIP and a fast-folding variant of pHLIP, in which each peptide is bound to a 1-palmitoyl-2-oleoylsn-glycero-3-phosphocholine (POPC) bilayer surface. Our results provide strong support for recently published spectroscopic studies, namely that pHLIP preferentially binds to the bilayer surface as a function of location of anionic amino acids and that backbone dehydration occurs upon binding. Unexpectedly, we also observed several instances of segments of pHLIP folding into a stable helical turn. Our results provide a molecular level of detail that is essential to providing new insights into pHLIP function and to facilitate design of variants with improved cell-penetrating capabilities.

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Section: Partitioning Of Phlip Influenced By Location Of Acidic Residuessupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Cooperative Non-bonded Forces Control Membrane Binding of the pH-Low Insertion Peptide pHLIP

Gupta

Ren

Mertz

2018

Preprint

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“…Other organic solvents frequently utilized for studying TM peptides include dimethyl sulfoxide (DMSO), methanol, ethanol, 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), and other hydrogenated or halogenated alcohols as well as mixtures of the above. A few TM peptides are also soluble in water and aqueous solutions, which is of great value for the quantitative description of spontaneous membrane insertion (Hunt et al, 1997b;Wimley and White, 2000;Reshetnyak et al, 2008; see also Sections 4.2 and 6.2) or hydrophobic partition equilibria (see Section 4.3).…”

Section: Isotropic Solventsmentioning

confidence: 99%

α-Helical transmembrane peptides: A “Divide and Conquer” approach to membrane proteins

Bordag¹,

Keller²

2010

Chemistry and Physics of Lipids

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“…LN pHe can be probed using pH indicators injected into either the tail vein or footpad (Fig S4A). The pH Low Insertion Peptide, pHLIP ® (21,22), conjugated to an 800 nm-emitting fluorescent dye (IR800), was injected into the footpad (40-60 µl of 40 µM), and LNs were harvested 24 hr later for ex vivo imaging.…”

Section: Fig 2f) Indicating a Lactate Transport Is A Protein (Mct) mentioning

confidence: 99%

Lymph Nodes Inhibit T-cell Effector Functions Locally by Establishing Acidic Niches

Estrella

Enríquez-Navas

et al. 2019

Preprint

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Lymph nodes are an essential component of the adaptive immune response where antigen-presenting cells are closely housed with their cognate effector cells. Protection of lymph node resident cells from activated immune cells in such close quarters would need to be robust and reversible. Effector functions of T-cells are profoundly and reversibly inhibited by an acidic microenvironment. The underlying

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Energetics Of Peptide (pHLIP) Binding To And Folding Across A Lipid Bilayer Membrane

Abstract: Andreev, O. A., Segala, M., Markin, V. S., & Engelman, D. M. (2008).Energetics of peptide (pHLIP) binding to and folding across a lipid bilayer membrane.

Cited by 14 publications

References 16 publications

Cooperative Non-bonded Forces Control Membrane Binding of the pH-Low Insertion Peptide pHLIP

Cooperative Non-bonded Forces Control Membrane Binding of the pH-Low Insertion Peptide pHLIP

α-Helical transmembrane peptides: A “Divide and Conquer” approach to membrane proteins

Lymph Nodes Inhibit T-cell Effector Functions Locally by Establishing Acidic Niches

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