Abstract
Latherin is a highly surface-active allergen protein found in the sweat and saliva of horses and other equids. Its surfactant activity is intrinsic to the protein in its native form, and is manifest without associated lipids or glycosylation. Latherin probably functions as a wetting agent in evaporative cooling in horses, but it may also assist in mastication of fibrous food as well as inhibition of microbial biofilms. It is a member of the PLUNC family of proteins abundant in the oral cavity and saliva of mammals, one of which has also been shown to be a surfactant and capable of disrupting microbial biofilms. How these proteins work as surfactants while remaining soluble and cell membrane-compatible is not known. Nor have their structures previously been reported. We have used protein nuclear magnetic resonance spectroscopy to determine the conformation and dynamics of latherin in aqueous solution. The protein is a monomer in solution with a slightly curved cylindrical structure exhibiting a ‘super-roll’ motif comprising a four-stranded anti-parallel β-sheet and two opposing α-helices which twist along the long axis of the cylinder. One end of the molecule has prominent, flexible loops that contain a number of apolar amino acid side chains. This, together with previous biophysical observations, leads us to a plausible mechanism for surfactant activity in which the molecule is first localized to the non-polar interface via these loops, and then unfolds and flattens to expose its hydrophobic interior to the air or non-polar surface. Intrinsically surface-active proteins are relatively rare in nature, and this is the first structure of such a protein from mammals to be reported. Both its conformation and proposed method of action are different from other, non-mammalian surfactant proteins investigated so far.
Highlights
Surfactants occur widely in nature, typically involving small molecules such as bile acids, or the glycolipids and phospholipids that, in complex with small proteins, comprise the pulmonary surfactants of mammalian lungs
Examples of surfactant proteins that exhibit strong surface activity in their native state and in the absence of associated lipids or glycosylation include the hydrophobins of fungi [5], a protein found in the foam nests of certain amphibians, and the subject of this report, the latherin protein of horses [3]
Latherin was originally described in the 1980s as an intrinsically surfaceactive, non-glycosylated protein that is abundant in horse sweat, and is the likely cause of the frothing seen in vigorously exercising animals [7]
Summary
Surfactants occur widely in nature, typically involving small molecules such as bile acids, or the glycolipids and phospholipids that, in complex with small proteins, comprise the pulmonary surfactants of mammalian lungs. Proteins themselves rarely exhibit intrinsic surfactant activity except when misfolded or denatured, as commonly seen in laboratory preparations, in food products or in some fire retardant foams. Latherin was originally described in the 1980s as an intrinsically surfaceactive, non-glycosylated protein that is abundant in horse sweat, and is the likely cause of the frothing seen in vigorously exercising animals [7]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call