Investigating molecular recognition and biological function at interfaces using piscidins, antimicrobial peptides from fish.
We studied amidated and non-amidated piscidins 1 and 3, amphipathic cationic antimicrobial peptides from fish, to characterize functional and structural similarities and differences between these peptides and better understand the structural motifs involved in biological activity and functional diversity among amidated and non-amidated isoforms. Antimicrobial and hemolytic assays were carried out to assess their potency and toxicity, respectively. Site-specific high-resolution solid-state NMR orientational restraints were obtained from (15)N-labeled amidated and non-amidated piscidins 1 and 3 in the presence of hydrated oriented lipid bilayers. Solid-state NMR and circular dichroism results indicate that the peptides are alpha-helical and oriented parallel to the membrane surface. This orientation was expected since peptide-lipid interactions are enhanced at the water-bilayer interface for amphipathic cationic antimicrobial peptides. (15)N solid-state NMR performed on oriented samples demonstrate that piscidin experiences fast, large amplitude backbone motions around an axis parallel to the bilayer normal. Under the conditions tested here, piscidin 1 was confirmed to be more antimicrobially potent than piscidin 3 and antimicrobial activity was not affected by amidation. In light of functional and structural similarities between piscidins 1 and 3, we propose that their topology and fast dynamics are related to their mechanism of action.
Chekmenev
Eduard Y
EY
National High Magnetic Field Laboratory, Center for Interdisciplinary Magnetic Resonance, 1800 E. Paul Dirac Drive, Tallahassee, FL 32310, USA.
Vollmar
Breanna S
BS
Forseth
Kristen T
KT
Manion
McKenna N
MN
Jones
Shiela M
SM
Wagner
Tim J
TJ
Endicott
RaeLynn M
RM
Kyriss
Brandon P
BP
Homem
Lorraine M
LM
Pate
Michelle
M
He
Jing
J
Raines
Joshua
J
Gor'kov
Peter L
PL
Brey
William W
WW
Mitchell
Dan J
DJ
Auman
Ann J
AJ
Ellard-Ivey
Mary J
MJ
Blazyk
Jack
J
Cotten
Myriam
M
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002942:Circular Dichroism; D005399:Fishes; D006461:Hemolysis / Q000187:drug effects; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
D000890:Anti-Infective Agents; D010455:Peptides