Models of buffering of dosage imbalances in protein complexes.
BACKGROUND
Stoichiometric imbalances in macromolecular complexes can lead to altered function. Such imbalances stem from under- or over-expression of a subunit of a complex consequent to a deletion, duplication or regulatory mutation of an allele encoding the relevant protein. In some cases, the phenotypic perturbations induced by such alterations can be subtle or be lacking because nonlinearities in the process of protein complex assembly can provide some degree of buffering.


RESULTS
We explore with biochemical models of increasing plausibility how buffering can be elicited. Specifically, we analyze the formation of a dimer AB and show that there are particular sets of parameters so that decreasing/increasing the input amount of either A or B translates into a non proportional (buffered) change of AB. The buffer effect also appears in higher-order structures provided that there are intermediate subcomplexes in the assembly process.


CONCLUSIONS
We highlight the importance of protein degradation and/or conformational inactivation for buffering to appear. The models sketched here have experimental support but can be further tested with existing biological resources.
Institut Jacques Monod, 15 rue Hélène Brion, 75013, Paris, France. veitia.reiner@ijm.univ-paris-diderot.fr.|Université Paris Diderot, Paris, France. veitia.reiner@ijm.univ-paris-diderot.fr.
Reiner A
RA
Veitia
University of Missouri, Division of Biological Sciences, Columbia, MO, 65211, USA. BirchlerJ@missouri.edu.
James A
JA
Birchler
D018628:Gene Dosage; D008957:Models, Genetic; D046912:Multiprotein Complexes / Q000235:genetics* / Q000378:metabolism; D009154:Mutation
D046912:Multiprotein Complexes