Linking New Paradigms in Protein Chemistry to Reversible Membrane-Protein Interactions
Pp. 3-57 (55)
Øyvind Halskau, Arturo Muga and Aurora Martínez
Amphitropic proteins are soluble, globular proteins that may − under certain
conditions − interact reversibly with a plasma membrane. How this apparent duality in
the properties of a protein is achieved has been a relatively little-studied subject until
recently. In this review we aim to summarize the current knowledge regarding some
important amphitropic systems in which the interaction with the membrane does not
require post-translational functional groups, but is an intrinsic property of the protein.
We discuss mechanisms and driving forces involved in membrane binding in the
context of two related concepts in protein folding and function that appear to have
implications for understanding the association of proteins with membranes. First, the
existence of some proteins with low-energy barrier heights for protein folding. Low
folding barriers and the ability of proteins to form stable molten globule states are
rationales that can explain how a protein can gain access to an ensemble (or continuum)
of non-native conformations that are competent membrane binders. Second, the focus
on order-disorder and disorder-order transitions to explain protein function, a concept
which has been mainly developed within the novel protein trinity paradigm. Here,
protein function can arise from any of three thermodynamic states: a solid, crystal-like
state; a dense fluid state; and an extended disordered state. Together these concepts aid
to understand amphitropic mechanism and to unify interpretations of protein behaviour
with respect to the degree of folding or unfolding of the membrane-bound proteins.
Protein-membrane, amphitropic proteins, the protein trinity, liposomes,
bicelles, micelles, transmembrane, membrane penetration, phospholipids,
amphitropic mechanism, charge, intrinsically disordered proteins.
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway.