Feminizing chicks a model for avian sex determination based on titration of Hint enzyme activity and the predicted structure of an Asw-Hint heterodimer.docVIP

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Feminizing chicks a model for avian sex determination based on titration of Hint enzyme activity and the predicted structure of an Asw-Hint heterodimer.doc

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Feminizing chicks a model for avian sex determination based on titration of Hint enzyme activity and the predicted structure of an Asw-Hint heterodimer

Open Access Research Feminizing chicks: a model for avian sex determination based on titration of Hint enzyme activity and the predicted structure of an Asw-Hint heterodimer Helen C Pace and Charles Brenner Address: Structural Biology and Bioinformatics Program, Kimmel Cancer Center, Philadelphia, PA 19107, USA. Correspondence: Charles Brenner. E-mail: brenner@ Published: 17 February 2003 Received: 28 October 2002 Revised: 3 January 2003 Accepted: 10 January 2003 Genome Biology 2003, 4:R18 The electronic version of this article is the complete one and can be found online at /2003/4/3/R18 ? 2003 Pace and Brenner; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the articles original URL. Abstract Background: In birds and some lizards, females are heterogametic with a ZW karyotype, while males are ZZ homogametes. The molecular basis for sexual differentiation in birds is unknown: arguments exist for doses of Z masculinizing chicks and for W information feminizing. ASW was identified as a tandemly repeated gene conserved on avian W chromosomes that is expressed in early female development and appears to be an inactive form of avian Z-encoded HINT. Hint is a dimeric enzyme that hydrolyzes AMP linked to lysine, whose enzyme activity is required for regulation of the Cdk7 homologous Kin28 kinase in yeast. Of 16 residues most conserved across all life forms for AMP interactions, 15 are sexually dimorphic in birds, that is, altered in the female-specific Asw protein. Genomic and expression data suggest that Asw may feminize chicks, dominantly interfering with Hint function by heterodimerization. Results: We consider whether positive cooperativity could explain how Hint heterodimerization with an inert enzyme might reduce specific activity by more than