Lipid membrane interaction and antimicrobial activity of GsMTx-4, an inhibitor of mechanosensitive channel.
GsMTx-4, a polypeptide from the spider Grammostola spatulata, is an inhibitor of mechanosensitive channels. It is known to interact with lipid membranes, suggesting it partitions into the membrane to alter the channel gating, but the effect of the membrane charge on GsMTx-4 activity remains unknown. In this study, we found that GsMTx-4 more effectively interacts with anionic lipids than zwitterionic ones. The effect of GsMTx-4 on negatively charged membranes was similar to that of the antimicrobial peptide melittin, which led us to assess GsMTx-4's antimicrobial activity. Interestingly, we found that, in contrast to other neurotoxins, GsMTx-4 exhibited antimicrobial properties and was more active against Gram-positive than Gram-negative bacteria. These results suggest that GsMTx-4 exerts its antimicrobial effect by altering the packing of the membrane and/or inhibiting mechanosensitive channels. These findings could point the way towards a new class of antimicrobial peptides.
Jung
Hoi Jong
HJ
Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, 500-712, Republic of Korea.
Kim
Pyoung Il
PI
Lee
Seung Kyu
SK
Lee
Chul Won
CW
Eu
Young-Jae
YJ
Lee
Dong Gun
DG
Earm
Yung-E
YE
Kim
Jae Il
JI
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D036341:Intercellular Signaling Peptides and Proteins; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008465:Mechanoreceptors / Q000187:drug effects*; D008563:Membrane Lipids / Q000378:metabolism*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D010713:Phosphatidylcholines / Q000378:metabolism*; D010715:Phosphatidylglycerols / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013111:Spider Venoms / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D036341:Intercellular Signaling Peptides and Proteins; D007473:Ion Channels; C411249:MTx4 protein, Grammostola spatulata; D008563:Membrane Lipids; D010455:Peptides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D013111:Spider Venoms; D014118:Toxins, Biological; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; D002118:Calcium; C028694:1-palmitoyl-2-oleoylphosphatidylcholine