title: Allosteric conformational barcodes direct signaling in the cell.
abstract: The cellular network is highly interconnected. Pathways merge and diverge. They proceed through shared proteins and may change directions. How are cellular pathways controlled and their directions decided, coded, and read? These questions become particularly acute when we consider that a small number of pathways, such as signaling pathways that regulate cell fates, cell proliferation, and cell death in development, are extensively exploited. This review focuses on these signaling questions from the structural standpoint and discusses the literature in this light. All co-occurring allosteric events (including posttranslational modifications, pathogen binding, and gain-of-function mutations) collectively tag the protein functional site with a unique barcode. The barcode shape is read by an interacting molecule, which transmits the signal. A conformational barcode provides an intracellular address label, which selectively favors binding to one partner and quenches binding to others, and, in this way, determines the pathway direction, and, eventually, the cell's response and fate.
authors.affiliation: Basic Science Program, SAIC-Frederick, Inc., Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA; Sackler Institute of Molecular Medicine, Department of Human Genetics and Molecular Medicine, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: nussinor@helix.nih.gov.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Buyong
authors.initials: B
authors.lastname: Ma
authors.forename: Chung-Jung
authors.initials: CJ
authors.lastname: Tsai
authors.forename: Peter
authors.initials: P
authors.lastname: Csermely
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D020134:Catalytic Domain; D048049:Extracellular Signal-Regulated MAP Kinases / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D010766:Phosphorylation; D060066:Protein Interaction Maps; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D048049:Extracellular Signal-Regulated MAP Kinases