![]() Many naturally occurring peptides bind to biological membranes, examples include peptide hormones, bacterial toxins and antimicrobial peptides with the latter being probably the largest and best characterized group of them. A variety of either linear or cyclic antimicrobial peptides have been described to date and they often provide a first unspecific defense mechanism against microbial invasion. ![]() Many of these peptides are believed to target microbial cytosolic cell membranes, disrupting them upon interaction. Besides knowing the structure, deciphering the mode of interaction with membranes or membrane-mimetics is necessary to understand their function. While the target of many antimicrobial peptides is the microbial lipid bilayer itself, membrane-binding peptide hormones and bacterial toxins likely act on proteins located in the membrane. Besides membrane-bound peptides, which can be structurally characterized easily by solution NMR spectroscopy, there are an enormous number of membrane-binding proteins. Although the 3D structure determination of soluble proteins by X-ray crystallography and NMR spectroscopy is well-established, far fewer structures of membrane-bound proteins have been solved to date. Structural studies of membrane proteins are considerably complicated by their amphipathic or hydrophobic nature and resulting solubility problems in aqueous buffers. Less than 2% of all structures in the Protein Data Bank (PDB) are membrane-bound proteins although they account for about 30% of all expressed proteins.įrequently, their limited stability in the absence of lipids constitutes an additional problem. Noteworthy, about 45% of all pharmaceuticals target G-protein coupled receptors, which are also a group of membrane-bound proteins. ![]() The limited structural information available for these proteins stems either from difficulties in crystallization or their large size, resulting in broad signals and limited spectral dispersion in NMR spectra.
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