English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Crystal structure and functional mechanism of a human antimicrobial membrane channel.

Song, C., Weichbrodt, C., Salnikov, E., Dynowski, M., Forsberg, B., Bechinger, B., et al. (2013). Crystal structure and functional mechanism of a human antimicrobial membrane channel. Proceedings of the National Academy of Sciences of the United States of America, 110(12), 4586-4591. doi:10.1073/pnas.1214739110.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-EB45-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CDE4-B
Genre: Journal Article

Files

show Files
hide Files
:
1703486.pdf (Publisher version), 964KB
Name:
1703486.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1703486_SI.pdf (Publisher version), 2MB
Name:
1703486_SI.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1703486_sm01.avi (Supplementary material), 8MB
Name:
1703486_sm01.avi
Description:
-
Visibility:
Public
MIME-Type / Checksum:
video/x-msvideo / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-
:
1703486_sm02.avi (Supplementary material), 6MB
Name:
1703486_sm02.avi
Description:
-
Visibility:
Public
MIME-Type / Checksum:
video/x-msvideo / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show
hide
Description:
-

Creators

show
hide
 Creators:
Song, C.1, Author              
Weichbrodt, C., Author
Salnikov, E., Author
Dynowski, M., Author
Forsberg, B., Author
Bechinger, B., Author
Steinem, C., Author
de Groot, B. L.1, Author              
Zachariae, U., Author
Zeth, K., Author
Affiliations:
1Research Group of Computational Biomolecular Dynamics, MPI for biophysical chemistry, Max Planck Society, ou_578573              

Content

show
hide
Free keywords: -
 Abstract: Multicellular organisms fight bacterial and fungal infections by producing peptide-derived broad-spectrum antibiotics. These host-defense peptides compromise the integrity of microbial cell membranes and thus evade pathways by which bacteria develop rapid antibiotic resistance. Although more than 1,700 host-defense peptides have been identified, the structural and mechanistic basis of their action remains speculative. This impedes the desired rational development of these agents into next-generation antibiotics. We present the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology, and MD simulations of human dermcidin in membranes that reveal the antibiotic mechanism of this major human antimicrobial, found to suppress Staphylococcus aureus growth on the epidermal surface. Dermcidin forms an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidate the unusual membrane permeation pathway for ions and show adjustment of the pore to various membranes. Our study unravels the comprehensive mechanism for the membrane-disruptive action of this mammalian host-defense peptide at atomistic level. The results may form a foundation for the structure-based design of peptide antibiotics.

Details

show
hide
Language(s): eng - English
 Dates: 2013-02-202013-03-19
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1073/pnas.1214739110
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 110 (12) Sequence Number: - Start / End Page: 4586 - 4591 Identifier: -