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Molecular Codes Through Complex Formation in a Model of the Human Inner Kinetochore

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Abstract

We apply molecular code theory to a rule-based model of the human inner kinetochore and study how complex formation in general can give rise to molecular codes. We analyze 105 reaction networks generated from the rule-based inner kinetochore model in two variants: with and without dissociation of complexes. Interestingly, we found codes only when some but not all complexes are allowed to dissociate. We show that this is due to the fact that in the kinetochore model proteins can only bind at kinetochores by attaching to already attached proteins and cannot form complexes in free solution. Using a generalized linear mixed model we study which centromere protein (CENP) can take which role in a molecular code (sign, meaning, context). By this, associations between CENPs (CenpA, CenpQ, CenpU and CenpI) and code roles are found. We observed that CenpA is a major risk factor (increases probability for code role) while CenpQ is a major protection factor (decreases probability for code role). Finally we show, using an abstract model of copolymer formation, that molecular codes can also be realized solely by the formation of stable complexes, which do not dissociate. For example, with particular dimers as context a molecular code mapping from two different monomers to two particular trimers can be realized just by non-selective complex formation. We conclude that the formation of protein complexes can be utilized by the cell to implement molecular codes. Living cells thus facilitate a subsystem allowing for an enormous flexibility in the realization of mappings, which can be used for specific regulatory processes, e.g. via the context of a mapping.

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Notes

  1. External in the sense of the code, i.e. not the signs, or contexts itself.

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Authors and Affiliations

  1. Institute of Biostatistics and Clinical Research, University of Muenster, Muenster, Germany

    Dennis Görlich

  2. Bio Systems Analysis Group, Institute of Computer Science, Jena Center for Bioinformatics and, Friedrich Schiller University Jena, Jena, Germany

    Gabi Escuela, Gerd Gruenert, Peter Dittrich & Bashar Ibrahim

  3. Umm Al-Qura University, University College in Al-Qunfudah, Makkah Al-Mukarramah, Kingdom of Saudi Arabia

    Bashar Ibrahim

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  1. Dennis Görlich
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  2. Gabi Escuela
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  3. Gerd Gruenert
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  4. Peter Dittrich
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  5. Bashar Ibrahim
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Correspondence to Dennis Görlich.

Additional information

This work was supported by the German Research Foundation priority programs InKoMBio (SPP 1395, Grant DI 852/10-1), the European Commission NeuNeu Project (248992) and the Jena School for Microbial Communication (JSMC).

Appendix

Appendix

Fig. 9
figure 9

Forest plot of the odds ratios and 95 %-confidence intervals of the GLMM for response CODE.

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Fig. 10
figure 10

Forest plot of the odds ratios and 95 %-confidence intervals of the GLMM for response SIGN

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Table 4 Odd ratio estimates of the generalized linear mixed model for the response SIGN
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Fig. 11
figure 11

Forest plot of the odds ratios and 95 %-confidence intervals of the GLMM for response MEANING

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Table 5 Odd ratio estimate of the generalized linear mixed model for the response MEANING
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Fig. 12
figure 12

Forest plot of the odds ratios and 95 %-confidence intervals of the GLMM for response CONTEXT

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Table 6 Odd ratio estimates of the generalized linear mixed model for the response CONTEXT
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Görlich, D., Escuela, G., Gruenert, G. et al. Molecular Codes Through Complex Formation in a Model of the Human Inner Kinetochore. Biosemiotics 7, 223–247 (2014). https://doi.org/10.1007/s12304-013-9193-5

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