Recently, we demonstrated that each SBD contains a subset of key amino acid residues that are physically involved in glycolipid binding. Identifying these residues and understanding why they confer a particular specificity for a given SBD/glycolipid couple is a critical step to elucidate the molecular mechanisms controling protein/glycolipid interactions. In this respect, we have recently proposed that these interactions are governed by a biochemical code and that a rational strategy to decipher this code is to study protein/glycolipid interactions with minimal synthetic SBD peptides. In the present study we have used both wild-type and mutant peptides derived from the respective SBDs of Ab and a-synuclein. Through a combination of in silico, physico-chemical, and cellular approaches, we have dissected the molecular mechanisms accounting for the ganglioside-binding specificity of Ab and a-synuclein. These results have enabled us to create a chimeric a-synuclein/Ab peptide displaying the ganglioside-binding properties of both proteins. Our knowledge of glycolipid-protein interactions has rapidly grown since the discovery in 2002 of a common structural domain in sphingolipid-binding proteins, referred to as the SBD. A broad range of SBDs have been identified in phylogeneticallydistant proteins including microbial, insect and human proteins. These discoveries have enabled to draw a photofit of the SBD, which is typically a looped domain with a central aromatic residue and a basic amino acid at each end. Then subtle variations in the amino acid sequence of the SBD may confer distinct glycolipid-binding properties, as illustrated for Ab and a-synuclein.. This complicates the elucidation of the code that controls glycolipid/protein interactions. Despite this intrinsic difficulty, we took advantage of the fact that many SBD-derived synthetic peptides retained the glycolipid-binding specificity of the full-length proteins from which they originate. The possibility to assess the interaction of short synthetic peptides with glycolipid-containing artificial membranes considerably accelerated our comprehension of the molecular mechanisms controling glycolipid recognition by proteins. The use of Langmuir monolayers allowed to precisely control the molar ratio of glycolipids in lipid mixtures, and, most importantly, to assess the role of cholesterol in protein-glycolipid interactions. In the present report, we have designed a series of 12-mer peptides derived from Ab and a-synuclein proteins, and analyzed the insertion of these peptides into ganglioside monolayers. This strategy allowed us to deciphering the biochemical code governing the specificity of interaction of these amyloid proteins with distinct plasma membrane gangliosides: GM1 for Ab and GM3 for asynuclein. Streptomycetes are soil-dwelling Gram-positive bacteria that have a large linear chromosome with high GC content, containing a central region that is highly conserved throughout the genus, and CYT 11387 terminal regions that are variable in composition and organization. Streptomyces species secreted large quantities of proteins via the general secretory pathway and twin-arginine translocation pathway to their living niches.