Editorial: Peptide-membrane structure and interactions

Abstract

Membrane proteins play the central roles in cellular processes ranging from nutrient uptake and signaling, to cell–cell communication. A significant number of human diseases are caused by an imbalance, a mutation, or a depletion in the membrane proteins of cells; for example, critical mutations in the membrane-spanning domains of these proteins underlie the causes of many human diseases, including some forms of cancer and diabetes, and cystic fibrosis. Indeed, the rational design of membrane proteins with modified properties is a highly desirable goal for development of therapies through molecular bioinformatics and biotechnology. Furthermore, virtually all drugs now in use must at one point in their administration cross a biological membrane; thus, the membrane is a fundamental target in drug design. However, one cannot deduce the molecular mechanisms of a disease, or move directly toward drug design/therapy, until the detailed interactions of peptides and proteins with membranes—and the structures these interactions produce—have been described in a systematic manner. In view of the timeliness of research in these areas, the ‘7th Naples Workshop on Bioactive Peptides’, held jointly with the ‘2nd Peptide Engineering Meeting’, in Anacapri, Italy on Sept. 5–8, 2000, invited plenary lectures by leading practitioners in these research areas. The papers in this issue of Peptide Science were developed from these presentations. In the first paper, Epand and Epand use viral fusion peptides in studies aimed at understanding how membrane intrinsic curvature affects the insertion of peptides or proteins in membranes, and how in turn, the physical properties of the membrane modulate the conformation and activity of proteins that bind to membranes. In further studies of peptide conformation and orientation in lipid bilayers, Voyer and his group present a description of some novel crown ring peptides designed to mimic natural ion channel proteins. Ruysschaert and his associates discuss the potentialities of attenuated total reflection (ATR) infra-red spectroscopy for determination of the orientation of membrane-interactive components, and of ligand-induced tertiary structural features in reconstituted membrane proteins. Hitz and Luisi address the phenomenon of membrane-assisted selective polycondensation of amino acids and peptides, examining whether the membrane matrix allows the formation of hydrophobic peptides, which could not otherwise be obtained, in aqueous solution. Kimura and his group present studies of cation recognition through self-assembled monolayers of helical peptides having a crown ether unit, using the techniques of impedance spectroscopy and cyclic voltammetry. Kobayashi, Yamazaki, and their co-workers locate key residues in the extracellular ligand-binding domain of wild type and mutant bone morphogenetic protein (BMP) receptors, with BMP affinities determined by surface plasmon resonance biosensor techniques. In the final paper, Tanaka and co-workers manipulate selected hydrophobic positions in de novo designed trimeric coiled coil peptides to confer new, desirable properties and functions to these systems. The diversity of these approaches reinforces the notion that a broadly-based arsenal of techniques will be the most successful strategy for deducing the general principles, which guide membrane structure/function and the mutual impact of the specific properties of hydrophobic peptides and membranes. Hopefully, this issue of Peptide Science will find an equally-broad readership.