Title:Intrinsic Disorder in Male Sex Determination: Disorderedness of Proteins from the Sry Transcriptional Network
Volume: 18
Issue: 5
Author(s): Jean Merone, Onyekahi Nwogu, Jennifer M. Redington and Vladimir N. Uversky
Affiliation:
Keywords:
Sex determination, Sry pathway, intrinsically disordered proteins, protein-protein interactions, posttranslational
modifications, binding induced folding, polymorphysm, protein structure, protein function.
Abstract: Sex differentiation is a complex process where sexually indifferent embryo progressively
acquires male or female characteristics via tightly controlled, perfectly timed, and sophisticatedly intertwined
chain of events. This process is controlled and regulated by a set of specific proteins, with
one of the first steps in sex differentiation being the activation of the Y-chromosomal Sry gene (sexdetermining
region Y) in males that acts as a switch from undifferentiated gonad somatic cells to testis
development. There are several key players in this process, which constitute the Sry transcriptional
network, and collective action of which governs testis determination. Although it is accepted now that
many proteins engaged in signal transduction as well as regulation and control of various biological
processes are intrinsically disordered (i.e., do not have unique structure and remain unstructured, or
incompletely structured, under physiological conditions), the roles and profusion of intrinsic disorder
in proteins involved in the male sex determination have not been accessed as of yet. The goal of this
study is to cover this gap by analyzing some key players of the Sry transcriptional network. To this
end, we employed a broad set of computational tools for intrinsic disorder analysis and conducted intensive
literature search in order to gain information on the structural peculiarities of the Sry networkrelated
proteins, their intrinsic disorder predispositions, and the roles of intrinsic disorder in their functions.
