Understanding large multiprotein complexes: applying a multiple allosteric networks model to explain the function of...

Area of Science:

• Molecular Biology
• Biochemistry
• Systems Biology

Background:

• Multi-subunit protein complexes regulate crucial cellular processes, including transcription.
• These complexes act as platforms connecting DNA-binding activators to promoters.
• The precise function, subunit organization, and molecular basis of these complexes remain incompletely understood.

Purpose of the Study:

• To elucidate the functional roles of multi-subunit protein complexes.
• To explain the molecular basis for subunit function and organization within complexes.
• To investigate the reasons behind specific subunit interconnections.

Main Methods:

• Development of a network allostery model.
• Application of the model to the eukaryotic RNA polymerase II Mediator complex.
• Analysis of information transfer through conformational spread within functional networks.

Main Results:

• The multiple allosteric networks model (MANM) proposes protein complexes function as interconnected networks.
• Information transfer occurs via subunit-to-subunit propagation of an allosteric state (conformational spread).
• Distinct sub-networks within the Mediator complex possess discrete, activatable functions.

Conclusions:

• Multi-subunit complexes like Mediator are organized as functional networks, not just physical assemblies.
• Conformational spread is a key mechanism for information transfer within these complexes.
• Subunit interactions define functional sub-networks crucial for regulating transcription.