Choline-binding modules (CBMs) have a ββ-solenoid structure composed of choline-binding repeats (CBR), which consist of a β-hairpin followed by a short linker. To find minimal peptides that are able to maintain the CBR native structure and to evaluate their remaining choline-binding ability, we have analysed the third β-hairpin of the CBM from the pneumococcal LytA autolysin. Circular dichroism and NMR data reveal that this peptide forms a highly stable native-like β-hairpin both in aqueous solution and in the presence of trifluoroethanol, but, strikingly, the peptide structure is a stable amphipathic α-helix in both zwitterionic (dodecylphosphocholine) and anionic (sodium dodecylsulfate) detergent micelles, as well as in small unilamellar vesicles. This β-hairpin to α-helix conversion is reversible. Given that the β-hairpin and α-helix differ greatly in the distribution of hydrophobic and hydrophilic side chains, we propose that the amphipathicity is a requirement for a peptide structure to interact and to be stable in micelles or lipid vesicles. To our knowledge, this “chameleonic” behaviour is the only described case of a micelle-induced structural transition between two ordered peptide structures.

Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation, reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually, cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed. In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present.

A novel inhibitor of interactions between signaling proteins in T cells demonstrates promising preventive and therapeutic effects in several models of autoimmune disease.

Aut6noma de Madrid, Cantoblanco Madfid 28049 and 'Instituto de Estructura de la Materia, CSIC, Serrano 119, Madrid 28006, Spain 2Corresponding author Communicated by H.R.B.PelhamThe CD3-r endoplasmic reticulum (ER) retention motif has been characterized by mutagenesis and NMR spectroscopy. Iyr177, Leul80 and Argl83 are involved in ER retention. The motif forms an elongated a-helix in which the tyrosine and leucine residues are closely apposed, followed by a PI' turn that places Argl83 in the vicinity of Leul80. The structure formed by Tyrl77 and the leucine in position +3 is reminiscent of the Pturn structure adopted by tyrosine-containing endocytosis signals. Moreover, substitution of the transferrin receptor (TffR) internalization sequence by the CD3-F motif still allowed the rapid internalization of the TffR and, conversely, the chimeric protein resulting from the substitution of the CD3-e motif by the endocytosis signal of the low density lipoprotein receptor was ER located. These data support the idea of a functional homology between the two types of signal.