A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1
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 ha...
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2016-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716305502 |
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doaj-5f16ba8789c145e3a7460853e19587122020-11-25T02:21:15ZengElsevierCell Reports2211-12472016-06-0115102097210810.1016/j.celrep.2016.04.088A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1Mauris C. Nnamani0Soumya Ganguly1Eric M. Erkenbrack2Vincent J. Lynch3Laura S. Mizoue4Yingchun Tong5Heather L. Darling6Monika Fuxreiter7Jens Meiler8Günter P. Wagner9Yale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USADepartments of Chemistry, Pharmacology and Biomedical Informatics, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USAYale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USADepartment of Human Genetics, The University of Chicago, 920 E. 58th Street, CLSC 319C, Chicago, IL 60637, USAHoward Hughes Medical Institute, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80303, USAYale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USADepartments of Chemistry, Pharmacology and Biomedical Informatics, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USAMTA-DE Momentum Laboratory of Protein Dynamics, University of Debrecen, 4032 Debrecen, Nagyerdei krt 98, HungaryDepartments of Chemistry, Pharmacology and Biomedical Informatics, Center for Structural Biology and Institute of Chemical Biology, Vanderbilt University, Nashville, TN 37232, USAYale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, CT 06511, USATranscription 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.http://www.sciencedirect.com/science/article/pii/S2211124716305502 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1 Cell Reports |
| author_facet |
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 |
| author_sort |
Mauris C. Nnamani |
| title |
A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1 |
| title_short |
A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1 |
| title_full |
A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1 |
| title_fullStr |
A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1 |
| title_full_unstemmed |
A Derived Allosteric Switch Underlies the Evolution of Conditional Cooperativity between HOXA11 and FOXO1 |
| title_sort |
derived allosteric switch underlies the evolution of conditional cooperativity between hoxa11 and foxo1 |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2016-06-01 |
| description |
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. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124716305502 |
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