Species right across the evolutionary scale from insects to mammals use peptides as part of their host-defense system to counter microbial infection. The primary structures of a large number of these host-defense peptides have been determined. While there is no primary structure homology, the peptides are characterized by a preponderance of cationic and hydrophobic amino acids. The secondary structures of many of the host-defense peptides have been determined by a variety of techniques. The acyclic peptides tend to adopt helical conformation, especially in media of low dielectric constant, whereas peptides with more than one disulfide bridge adopt beta-structures. Detailed investigations have indicated that a majority of these host-defense peptides exert their action by permeabilizing microbial membranes. In this review, we discuss structural and charge requirements for the interaction of endogenous antimicrobial peptides and short peptides that have been derived from them, with membranes.

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The store-operated calcium channel (SOC) located in the plasma membrane (PM) mediates capacitative entry of extracellular calcium after depletion of intracellular calcium stores in the endoplasmic or sarcoplasmic reticulum (ER/SR). An intimate interaction between the PM and the ER/SR is essential for the operation of this calcium signalling pathway. Mitsugumin 29 (MG29) is a synaptophysin-family-related protein located in the junction between the PM and SR of skeletal muscle. Here, we identify SOC in skeletal muscle and characterise its regulation by MG29 and the ryanodine receptor (RyR) located in the SR. Targeted deletion of mg29 alters the junctional membrane structure, causes severe dysfunction of SOC and SR calcium homeostasis and increases the susceptibility of muscle to fatigue stimulation. Severe dysfunction of SOC is also identified in muscle cells lacking both type 1 and type 3 RyRs, indicating that SOC activation requires an intact interaction between the PM and the SR, and is linked to conformational changes of RyRs. Whereas defective SOC seems to be inconsequential to short-term excitation-contraction coupling, the slow cumulative calcium entry through SOC is crucial for long-term calcium homeostasis, such that reduced SOC activity exaggerates muscle fatigue under conditions of intensive exercise.

The observation by Mueller and Rudin9 that alamethicin induces excitability in artificial lipid bilayer aroused tremendous interest in the study of alamethicin-lipid interactions. Studies on alamethicinmodified electrical conductance across lipid bilayers9"14 indicate that the mechanism by which ions are transported across lipid bilayers is by the formation of channels or pores, as in the case of gramicidin A. However, unlike gramicidin A, alamethicin shows a strong voltage-dependent conductance. Studies on the concentration dependence of the channel conductance suggest that 6-8 molecules may be involved in an aggregate.14 Further, the cation conductance by the peptide does not show any specificity. In spite of numerous reports,3,15 a clear picture regarding the molecular structure of the pores and the manner in which they modulate passage of ions through the bilayer has not yet emerged. Attempts to develop structure-Padmanabhan Balaram Is an Assistant Professor in the Molecular Biophy-

ities comparable to that of IL whereas ILF exhibits only poAbstract The antimicrobial and hemolytic activities of the 13-tent antimicrobial activity without any hemolytic activity. room temperature. The peptides were checked for purity on HPLC using a reverse-phase column (Bio Rad C4 Hi-Pore RP 304, 250 ×4.6 Key words: Indolicidin; Antimicrobial activity; Hemolytic mm), using a solvent system of 0.1% aqueous TFA and acetonitrile. activity; Membrane permeabilization All the peptides were > 90% pure. However, HPLC purified peptides were used for all studies. The peptides were characterized by amino acid and sequence analyses on a LKB 4151 Alpha plus analyser and 473A Applied Biosystems gas phase sequencer, respectively.