Open Access Highly Accessed Research article

Tetramer formation in Arabidopsis MADS domain proteins: analysis of a protein-protein interaction network

Carlos Espinosa-Soto12, Richard GH Immink3, Gerco C Angenent34, Elena R Alvarez-Buylla5* and Stefan de Folter1*

Author Affiliations

1 Laboratorio Nacional de Genómica para la Biodiversidad (Langebio), Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Km 9.6 Libramiento Norte Carretera León, C.P. 36821 Irapuato, Mexico

2 Current address: Instituto de Física, Universidad Autónoma de San Luis Potosí, Manuel Nava 6, Zona Universitaria, C.P. 78290 San Luis Potosí, Mexico

3 Plant Research International, 6700 AA Wageningen, The Netherlands

4 Laboratory of Molecular Biology, Wageningen University, 6700 AA Wageningen, The Netherlands

5 Departamento de Ecología Funcional. Instituto de Ecología, Universidad Nacional Autónoma de México, Ap. Postal 70-275, 3er Circ. Ext. Jto. Jard. Bot., CU, C.P. 04510 Mexico, D.F., Mexico

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BMC Systems Biology 2014, 8:9  doi:10.1186/1752-0509-8-9

Published: 27 January 2014



MADS domain proteins are transcription factors that coordinate several important developmental processes in plants. These proteins interact with other MADS domain proteins to form dimers, and it has been proposed that they are able to associate as tetrameric complexes that regulate transcription of target genes. Whether the formation of functional tetramers is a widespread property of plant MADS domain proteins, or it is specific to few of these transcriptional regulators remains unclear.


We analyzed the structure of the network of physical interactions among MADS domain proteins in Arabidopsis thaliana. We determined the abundance of subgraphs that represent the connection pattern expected for a MADS domain protein heterotetramer. These subgraphs were significantly more abundant in the MADS domain protein interaction network than in randomized analogous networks. Importantly, these subgraphs are not significantly frequent in a protein interaction network of TCP plant transcription factors, when compared to expectation by chance. In addition, we found that MADS domain proteins in tetramer-like subgraphs are more likely to be expressed jointly than proteins in other subgraphs. This effect is mainly due to proteins in the monophyletic MIKC clade, as there is no association between tetramer-like subgraphs and co-expression for proteins outside this clade.


Our results support that the tendency to form functional tetramers is widespread in the MADS domain protein-protein interaction network. Our observations also suggest that this trend is prevalent, or perhaps exclusive, for proteins in the MIKC clade. Because it is possible to retrodict several experimental results from our analyses, our work can be an important aid to make new predictions and facilitates experimental research on plant MADS domain proteins.

MADS domain proteins; Protein-protein interaction network; Transcription factors; Tetramers; Subgraph abundance; Arabidopsis thaliana