Kinetics of peptide folding in lipid membranes

Smith-Dupont, Kathryn B.; Markiewicz, Beatrice N.; Gai, Feng

doi:10.1002/bip.22640

Cited by 8 publications

(9 citation statements)

References 148 publications

(189 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lipid membranes are essential to numerous biological processes, and their multiple functions are rooted in their diverse interfacial environments (1)(2)(3)(4). On its own, a bilayer provides a nanometer-length gradient from a polar, aqueous environment at the interface to a nonpolar hydrophobic environment within the membrane center.…”

Section: Introductionmentioning

confidence: 99%

Site-Specific Peptide Probes Detect Buried Water in a Lipid Membrane

Flanagan

Baiz

2019

Biophysical Journal

View full text Add to dashboard Cite

Transmembrane peptides contain polar residues in the interior of the membrane, which may alter the electrostatic environment and favor hydration in the otherwise nonpolar environment of the membrane core. Here, we demonstrate a general, nonperturbative strategy to probe hydration of the peptide backbone at specific depths within the bilayer using a combination of site-specific isotope labels, ultrafast two-dimensional infrared spectroscopy, and spectral modeling based on molecular dynamics simulations. Our results show that the amphiphilic pH-low insertion peptide supports a highly heterogeneous environment, with significant backbone hydration of nonpolar residues neighboring charged residues. For example, a leucine residue located as far as 1 nm into the hydrophobic bulk reports hydrogen-bonded populations as high as $20%. These findings indicate that the polar nature of these residues may facilitate the transport of water molecules into the hydrophobic core of the membrane.

show abstract

Section: Introductionmentioning

confidence: 99%

Site-Specific Peptide Probes Detect Buried Water in a Lipid Membrane

Flanagan

Baiz

2019

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…This work reports the second stage of a three-stage project aiming at a more complete theoretical understanding of membrane-associated protein or peptide folding [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. The first stage, reported in Ref.…”

Section: Introductionmentioning

confidence: 99%

Free-energy landscapes and insertion pathways for peptides in membrane environment

Sharma,

Meyer,

Habeeb

et al. 2022

Preprint

View full text Add to dashboard Cite

Free-energy landscapes for short peptides -specifically for variants of the pH Low Insertion Peptide (pHLIP) -in the heterogeneous environment of a lipid bilayer or cell membrane are constructed, taking into account a set of dominant interactions and the conformational preferences of the peptide backbone. Our methodology interprets broken internal H-bonds along the backbone of a polypeptide as statistically interacting quasiparticles, activated from the helix reference state. The favored conformation depends on the local environment (ranging from polar to non-polar), specifically on the availability of external H-bonds (with H2O molecules or lipid headgroups) to replace internal H-bonds. The dominant side-chain contribution is accounted for by residue-specific transfer free energies between polar and non-polar environments. The free-energy landscape is sensitive to the level of pH in the aqueous environment surrounding the membrane. For high pH, we identify pathways of descending free energy that suggest a coexistence of membrane-adsorbed peptides with peptides in solution. A drop in pH raises the degree of protonation of negatively charged residues and thus increases the hydrophobicity of peptide segments near the C terminus. For low pH, we identify insertion pathways between the membrane-adsorbed state and a stable trans-membrane state with the C terminus having crossed the membrane.

show abstract

“…Therefore, a new approach is required to resolve the dynamics of peptide insertion, the coupled dynamics of the membrane, and any subsequent folding or oligomerization steps. 6 …”

mentioning

confidence: 99%

“…Therefore, a new approach is required to resolve the dynamics of peptide insertion, the coupled dynamics of the membrane, and any subsequent folding or oligomerization steps. 6 Some small linear peptides such as antimicrobial peptides (AMPs) are capable of spontaneous insertion into membranes. AMPs are typically short sequences of amino acids that yield amphipathic secondary structures with a net cationic charge.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Submillisecond Dynamics of Mastoparan X Insertion into Lipid Membranes

Schuler

Nagarajan

Dyer

2016

J. Phys. Chem. Lett.

View full text Add to dashboard Cite

The mechanism of protein insertion into a lipid bilayer is poorly understood because the kinetics of this process is difficult to measure. We developed a new approach to study insertion of the antimicrobial peptide Mastoparan X into zwitterionic lipid vesicles, using a laser-induced temperature-jump to initiate insertion on the microsecond time scale and infrared and fluorescence spectroscopies to follow the kinetics. Infrared probes the desolvation of the peptide backbone and yields biphasic kinetics with relaxation lifetimes of 12 and 117 μs, whereas fluorescence probes the intrinsic tryptophan residue located near the N-terminus and yields a single exponential phase with a lifetime of 440 μs. Arrhenius analysis of the temperature-dependent rates yields an activation energy for insertion of 96 kJ/mol. These results demonstrate the complexity of the insertion process and provide mechanistic insight into the interplay between peptides and the lipid bilayer required for peptide transport across cellular membranes.

show abstract

Kinetics of peptide folding in lipid membranes

Cited by 8 publications

References 148 publications

Site-Specific Peptide Probes Detect Buried Water in a Lipid Membrane

Site-Specific Peptide Probes Detect Buried Water in a Lipid Membrane

Free-energy landscapes and insertion pathways for peptides in membrane environment

Submillisecond Dynamics of Mastoparan X Insertion into Lipid Membranes

Contact Info

Product

Resources

About