title: Searching for protein signatures using a multilevel alphabet.
abstract: Short motifs are known to play diverse roles in proteins, such as in mediating the interactions with other molecules, binding to membranes, or conducting a specific biological function. Standard approaches currently employed to detect short motifs in proteins search for enrichment of amino acid motifs considering mostly the sequence information. Here, we presented a new approach to search for common motifs (protein signatures) which share both physicochemical and structural properties, looking simultaneously at different features. Our method takes as an input an amino acid sequence and translates it to a new alphabet that reflects its intrinsic structural and chemical properties. Using the MEME search algorithm, we identified the proteins signatures within subsets of protein which encompass common sequence and structural information. We demonstrated that we can detect enriched structural motifs, such as the amphipathic helix, from large datasets of linear sequences, as well as predicting common structural properties (such as disorder, surface accessibility, or secondary structures) of known functional-motifs. Finally, we applied the method to the yeast protein interactome and identified novel putative interacting motifs. We propose that our approach can be applied for de novo protein function prediction given either sequence or structural information.
authors: Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors: Ronit
authors: R
authors: Hod
authors: Refael
authors: R
authors: Kohen
authors: Yael
authors: Y
authors: Mandel-Gutfreund
mesh_terms: D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D030562:Databases, Protein; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D057386:Search Engine; D012984:Software; D048029:TNF Receptor-Associated Factor 6 / Q000737:chemistry / Q000378:metabolism; D015003:Yeasts / Q000737:chemistry / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D005656:Fungal Proteins; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D048029:TNF Receptor-Associated Factor 6