TY - JOUR
T1 - Allosteric conformational barcodes direct signaling in the cell
AU - Nussinov, Ruth
AU - Ma, Buyong
AU - Tsai, Chung Jung
AU - Csermely, Peter
N1 - Funding Information:
We are grateful to one of our reviewers, who provided a broad, insightful overview of our review, uniquely capturing its significance to the structural and signaling biology community and its implications to the field. We have incorporated it in the Conclusions with only minor modifications. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. It was also supported by research grants from the Hungarian National Science Foundation (OTKA K83314) and by the EU (TÁMOP-4.2.2/B-10/1-2010-0013). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research.
PY - 2013/9/3
Y1 - 2013/9/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84883480131&partnerID=8YFLogxK
U2 - 10.1016/j.str.2013.06.002
DO - 10.1016/j.str.2013.06.002
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C2 - 24010710
AN - SCOPUS:84883480131
SN - 0969-2126
VL - 21
SP - 1509
EP - 1521
JO - Structure
JF - Structure
IS - 9
ER -