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Cationic membrane peptides: atomic-level insight of structure–activity relationships from solid-state NMR

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Abstract

Many membrane-active peptides, such as cationic cell-penetrating peptides (CPPs) and antimicrobial peptides (AMPs), conduct their biological functions by interacting with the cell membrane. The interactions of charged residues with lipids and water facilitate membrane insertion, translocation or disruption of these highly hydrophobic species. In this review, we will summarize high-resolution structural and dynamic findings towards the understanding of the structure–activity relationship of lipid membrane-bound CPPs and AMPs, as examples of the current development of solid-state NMR (SSNMR) techniques for studying membrane peptides. We will present the most recent atomic-resolution structure of the guanidinium-phosphate complex, as constrained from experimentally measured site-specific distances. These SSNMR results will be valuable specifically for understanding the intracellular translocation pathway of CPPs and antimicrobial mechanism of AMPs, and more generally broaden our insight into how cationic macromolecules interact with and cross the lipid membrane.

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Abbreviations

AMP:

Antimicrobial peptide

CPP:

Cell-penetrating peptide

DARR:

Dipolar-assisted rotational resonance

DIPSHIFT:

Dipolar-chemical-shift correlation

DNP:

Dynamic nuclear polarization

H-bond:

Hydrogen bond

HETCOR:

Heteronuclear correlation

HNP-1:

Human neutrophil peptide-1

LPS:

Lipopolysaccharide

MAS:

Magic angle spinning

PE:

Phosphatidylethanolamine

PG:

Phosphatidylglycerol

PG-1:

Protegrin-1

POPC:

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine

POPE:

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine

POPG:

1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol

PRE:

Paramagnetic relaxation enhancement

PTD:

Protein transduction domain

REDOR:

Rotational-echo double-resonance

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Acknowledgments

The SSNMR research reviewed in this work was supported by grant GM066976 from National Institutes of Health (NIH) to M.H.

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  1. Yongchao Su

    Present address: Francis Bitter Magnet Laboratory and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA

Authors and Affiliations

  1. Department of Chemistry, Iowa State University, Ames, IA, 50011, USA

    Yongchao Su & Mei Hong

  2. Wuhan Institute of Physics and Mathematics, The Chinese Academy of Sciences, Wuhan, 430071, China

    Shenhui Li

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  1. Yongchao Su
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  2. Shenhui Li
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  3. Mei Hong
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Correspondence to Yongchao Su.

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Su, Y., Li, S. & Hong, M. Cationic membrane peptides: atomic-level insight of structure–activity relationships from solid-state NMR. Amino Acids 44, 821–833 (2013). https://doi.org/10.1007/s00726-012-1421-9

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  • DOI: https://doi.org/10.1007/s00726-012-1421-9

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