A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1

Mauris C. Nnamani; Soumya Ganguly; Eric M. Erkenbrack; Vincent J. Lynch; Laura S. Mizoue; Yingchun Tong; Heather L. Darling; Monika Fuxreiter; Jens Meiler; Günter P. Wagner

doi:10.1016/j.celrep.2016.04.088

Cell Reports (Jun 2016)

A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1

Mauris C. Nnamani,
Soumya Ganguly,
Eric M. Erkenbrack,
Vincent J. Lynch,
Laura S. Mizoue,
Yingchun Tong,
Heather L. Darling,
Monika Fuxreiter,
Jens Meiler,
Günter P. Wagner

Affiliations

Mauris C. Nnamani: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA
Soumya Ganguly: Departments of Chemistry, Pharmacology and Biomedical Informatics, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA
Eric M. Erkenbrack: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA
Vincent J. Lynch: Department of Human Genetics, The University of Chicago, 920 E. 58th Street, CLSC 319C, Chicago, IL 60637, USA
Laura S. Mizoue: Howard Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USA
Yingchun Tong: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA
Heather L. Darling: Departments of Chemistry, Pharmacology and Biomedical Informatics, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA
Monika Fuxreiter: MTA-DE Momentum Laboratory of Protein Dynamics, University of Debrecen, 4032 Debrecen, Nagyerdei krt 98, Hungary
Jens Meiler: Departments of Chemistry, Pharmacology and Biomedical Informatics, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USA
Günter P. Wagner: Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USA

DOI: https://doi.org/10.1016/j.celrep.2016.04.088
Journal volume & issue: Vol. 15, no. 10
pp. 2097 – 2108

Abstract

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Transcription factors (TFs) play multiple roles in development. Given this multifunctionality, it has been assumed that TFs are evolutionarily highly constrained. Here, we investigate the molecular mechanisms for the origin of a derived functional interaction between two TFs, HOXA11 and FOXO1. We have previously shown that the regulatory role of HOXA11 in mammalian endometrial stromal cells requires interaction with FOXO1, and that the physical interaction between these proteins evolved before their functional cooperativity. Here, we demonstrate that the derived functional cooperativity between HOXA11 and FOXO1 is due to derived allosteric regulation of HOXA11 by FOXO1. This study shows that TF function can evolve through changes affecting the functional output of a pre-existing protein complex.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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