Intrinsic Disorder in Male Sex Determination: Disorderedness of Proteins from the Sry Transcriptional Network.
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.
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, FL. United States.
Jean
J
Merone
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, FL. United States.
Onyekahi
O
Nwogu
Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida 33612, FL. United States.
Jennifer M
JM
Redington
Department of Molecular Medicine, University of South Florida, 12901 Bruce B. Downs Blvd. MDC07, Tampa, Florida 33612. United States.
Vladimir N
VN
Uversky
D000818:Animals; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D024282:Genes, sry; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D019849:Sex Determination Processes; D013737:Testis / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D064267:Intrinsically Disordered Proteins; D014157:Transcription Factors
Sex determination; Sry pathway; binding induced folding; intrinsically disordered proteins; polymorphysm; posttranslational
modifications; protein function.; protein structure; protein-protein interactions