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Computational analyses of the effect of novel amino acid clusters of human transglutaminase 2 on its structure and function

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Abstract

Transglutaminase 2 (TGM2) is a unique protein of a nine member family with several enzymatic and non-enzymatic activities and interacting partners. Its physiological and pathological roles, however, are not fully understood. Comparative genomic and computational analysis reported here have revealed phylogenetic changes of TGM2 resulting in novel amino acid clusters in humans and other primates, which may impact secondary structure and increase protein stability. These clusters are located in intrinsically disordered regions and via short linear motifs influence interactions with TGM2 partners directly, or through post-translation modification (phosphorylation and N-glycosylation sites). Our data shed new light on the structural background and evolution of TGM2 multi-functionality and points to so far unrevealed biological roles of the enzyme.

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Acknowledgments

This work was supported by the Research University Grant of the University of Debrecen (RH/885/2013), the Hungarian Scientific Research Fund (OTKA NK 105046), the New Hungary Development Plan via the TÁMOP-4.2.2.A-11/1/KONV-2012-0023 “VÉD-ELEM” project co-financed by the European Social Fund, the European Union Framework Programme 7 TRANSPATH ITN 289964 and the European Union and the State of Hungary, co-financed by the European Social Fund in the framework of the TÁMOP 4.2.4. A/2-11-1-2012-0001 ‘National Excellence Programme’ which provided personal support to R.K. The support of the Hungarian Scientific Research Fund (OTKA NN 106562) and the Momentum programme (LP2012-41) of the Hungarian Academy of Sciences is gratefully acknowledged (M.F.). The authors are grateful to Dr. Máté Demény for critically reading the manuscript.

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    Authors and Affiliations

    1. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Egyetem ter 1., Debrecen, 4012, Hungary

      Kiruphagaran Thangaraju, Róbert Király, János András Mótyán, Viktor Attila Ambrus, Mónika Fuxreiter & László Fésüs

    2. MTA-DE Momentum Laboratory of Protein Dynamics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

      Viktor Attila Ambrus & Mónika Fuxreiter

    3. MTA-DE Stem Cell, Apoptosis and Genomics Research Group of Hungarian Academy of Sciences, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

      László Fésüs

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    1. Kiruphagaran Thangaraju
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    2. Róbert Király
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    5. Mónika Fuxreiter
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    Correspondence to László Fésüs.

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    Handling Editors: S. Beninati, M. Piacentini, C. M. Bergamini.

    M. Fuxreiter and L. Fésüs contributed equally to this study.

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    Thangaraju, K., Király, R., Mótyán, J.A. et al. Computational analyses of the effect of novel amino acid clusters of human transglutaminase 2 on its structure and function. Amino Acids 49, 605–614 (2017). https://doi.org/10.1007/s00726-016-2330-0

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    • DOI: https://doi.org/10.1007/s00726-016-2330-0

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