Allosteric conformational barcodes direct signaling in the cell

Ruth Nussinov, Buyong Ma, Chung Jung Tsai, Peter Csermely

Research output: Contribution to journalReview article

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1509-1521
Number of pages13
JournalStructure
Volume21
Issue number9
DOIs
Publication statusPublished - Sep 3 2013

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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