Natively folded HypF-N and its early amyloid aggregates interact with phospholipid monolayers and destabilize supported phospholipid bilayers

¹ Department of Physics, University of Genoa, Italy
² Department of Biochemical Sciences, University of Florence, Italy

^* To whom correspondence should be addressed. E-mail: gliozzi{at}fisica.unige.it.

Submitted on May 23, 2006
Revised on July 6, 2006
Accepted on 22 August 2006

	Abstract

Recent data depict membranes as the main sites where proteins/peptides are recruited and concentrated, misfold and nucleate amyloids; at the same time, membranes are considered key triggers of amyloid toxicity. The N-terminal domain of the prokaryotic hydrogenase maturation factor HypF (HypF-N) in 30% trifluoroethanol undergoes a complex path of fibrillation starting with initial 2-3 nm oligomers and culminating with the appearance of mature fibrils. Oligomers are highly cytotoxic and permeabilize lipid membranes, both biological and synthetic. In this paper we report an in-depth study aimed at providing information on the surface activity of HypF-N and its interaction with synthetic membranes of different lipid composition either in the native conformation or as amyloid oligomers or fibrils. Like other amyloidogenic peptides, the natively folded HypF-N forms stable films at the air/water interface and inserts into synthetic phospholipid bilayers with efficiencies depending on the type of phospholipids. In addition, HypF-N pre-fibrillar aggregates interact with, insert into, and disassemble supported phospholipid bilayers similarly to other amyloidogenic peptides. These results support the idea that, at least in most cases, early amyloid aggregates of different peptides and proteins produce similar effects on the integrity of membrane assembly and hence on cell viability.

Key Words: amyloid, amyloid fibrils, bilayer destabilization, early amyloid aggregates, phospholipid monolayers, supported lipid bilayers