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Fuzziness pp 50-73 | Cite as

Interplay Between Protein Order, Disorder and Oligomericity in Receptor Signaling

  • Alexander B. Sigalov
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 725)

Abstract

Receptor-mediated signaling plays an important role in health and disease. Recent reports have revealed that many proteins that do not adopt globular structures under native conditions, thus termed intrinsically disordered, are involved in cell signaling. Intriguingly, physiologically relevant oligomerization of intrinsically disordered proteins (IDPs) has been recently observed and shown to exhibit unique biophysical characteristics, including the lack of significant changes in chemical shift and peak intensity upon binding. On the other hand, ligand-induced or - tuned receptor oligomerization is known to be a general feature of various cell surface receptors and to play a crucial role in signal transduction. In this work, I summarize several distinct features of protein disorder that are especially important as related to signal transduction. I also hypothesize that interactions of IDPs with their protein or lipid partners represent a general biphasic process with the electrostatic-driven „no disorder-to-order“ fast interaction which, depending on the interacting partner, may or may not be accompanied by the hydrophobic-driven slow formation of a secondary structure. Further, I suggest signaling-related functional connections between protein order, disorder and oligomericity and hypothesize that receptor oligomerization induced or tuned upon ligand binding outside the cell is translated across the membrane into protein oligomerization inside the cell, thus providing a general platform, the Signaling Chain HOmoOLigomerization (SCHOOL) platform, for receptor-mediated signaling. This structures our current multidisciplinary knowledge and views of the mechanisms governing the coupling of recognition to signal transduction and cell response. Importantly, this approach not only reveals previously unrecognized striking similarities in the basic mechanistic principles of function of numerous functionally diverse and unrelated surface membrane receptors, but also suggests the similarity between therapeutic targets, thus opening new horizons for both fundamental and clinically relevant studies.

Keywords

Natural Killer Cell Natural Killer Cell Receptor Protein Disorder Receptor Oligomerization Signal Trans Ducti 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2012

Authors and Affiliations

  • Alexander B. Sigalov
    • 1
  1. 1.SignaBlok, Inc.ShrewsburyUSA

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