A structurally plastic extension of the homeodomain recognition helix orchestrates central Hox protein activity
(English)Manuscript (preprint) (Other academic)
Protein function is encoded within the amino acid coding sequence and the variation in this sequence, and subsequent structure, provide the bases for functional diversification at the molecular and organismal levels. However, how separate protein domainscooperate to build protein activity remains largely unknown. Focusing on three domains of central Hox transcription factors, we mutagenized combinations of their domains to investigate their intrinsic functional organization. Our results demonstrate a high degree of domain interactivity, with an orchestrating role of a structurally plastic C-terminal extension of the homeodomain (HD). This domain provides, in a folding dependant manner, a topologically constrained contact with the Hox cofactor Extradenticle, which impacts the positioning of the recognition helix in the major groove of DNA. These findings provide novel insights in HD/DNA target recognition and, given the phylogeny of this C-terminal extension, also shed light on the molecular bases underlying the functional diversification of paralogous Hox families.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-63627OAI: oai:DiVA.org:liu-63627DiVA: diva2:381772