Abstract
Many peptides and proteins are attached to or immersed in a biological membrane. In order to understand their function not only the structure but also their topology in the membrane is important. Solution NMR spectroscopy is one of the most often used approaches to determine the orientation and localization of membrane-bound peptides and proteins. Here we give an application-oriented overview on the use of paramagnetic probes for the investigation of membrane-bound peptides and proteins. The examples discussed range from the large pool of antimicrobial peptides, bacterial toxins, cell penetrating peptides to domains of larger proteins or the calcium regulating protein phospholamban. Topological information is obtained in all these examples by the use of either attached or freely mobile paramagnetic tags. For some examples information obtained from the paramagnetic probes was included in the structure determination.
Highlights
Membrane-bound proteins and peptides constitute ~30% of all naturally occurring proteins and peptides [1]
Cysteine knots have been discovered in many different proteins including growth factors, inhibitory proteins and toxins and based on that three classes of such disulfide-rich proteins are distinguished, namely the Growth Factor Cysteine Knots (= GFCKs), the Inhibitor Cysteine Knots (= ICKs) and the Cyclic Cysteine Knots (= CCKs), whereby this review only focuses onto the last group being represented by the plant cyclotides [81]
16-doxylstearate, suggesting a binding close to the micelle surface [100]. With these studies on three different cyclotides from the two major subclasses it could be shown, that the global fold is conserved throughout the different families and that differences in the membrane binding mode and the orientation relative to the micelle surface are determined by differences in the presence of charged residues and the arrangement of hydrophobic surface patches
Summary
Membrane-bound proteins and peptides constitute ~30% of all naturally occurring proteins and peptides [1]. NMR is its size limitation, which makes obtaining atomic resolution structural information of large molecules or molecular assemblies very difficult This size limit could be significantly extended in the last dozens of years by techniques like transverse relaxation optimized spectroscopy (TROSY) [6] or selective, relaxation-optimized isotopic labeling [7], atomic resolution structural studies on systems above ~ 40 kDa are still rather challenging. For this reason membrane-bound peptides and proteins have to be studied using very small membrane-mimetics. Considering the huge number of such reports in the literature we have to restrict this overview to some, mainly recent, examples from different classes of peptides and proteins, many of which report on new methodological advances in the field
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