SRY and human sex determination: the basic tail of the HMG box functions as a kinetic clamp to augment DNA bending

Journal of Molecular Biology
Nelson B PhillipsMichael A Weiss

Abstract

Human testis-determining factor SRY contains a high-mobility-group (HMG) box, an alpha-helical DNA-binding domain that binds within an expanded minor groove to induce DNA bending. This motif is flanked on the C-terminal end by a basic tail, which functions both as a nuclear localization signal and accessory DNA-binding element. Whereas the HMG box is broadly conserved among otherwise unrelated transcription factors, tails differ in sequence and mode of DNA binding. Contrasting examples are provided by SRY and lymphoid enhancer factor 1 (LEF-1): whereas the SRY tail remains in the minor groove distal to the HMG box, the LEF-1 tail binds back across the center of the bent DNA site. The LEF-1 tail relieves electrostatic repulsion that would otherwise be incurred within the compressed major groove to enable sharp DNA bending with high affinity. Here, we demonstrate that the analogous SRY tail functions as a "kinetic clamp" to regulate the lifetime of the bent DNA complex. As in LEF-1, partial truncation of the distal SRY tail reduces specific DNA affinity and DNA bending, but these perturbations are modest: binding is reduced by only 1.8-fold, and bending by only 7-10 degrees . "Tailed" and truncated SRY complexes exhibit similar s...Continue Reading

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Citations

Oct 31, 2009·Journal of Applied Genetics·R P Piprek
Mar 24, 2009·Journal of Biochemistry·Shigeharu TakiyaKeiichi Kawano
Dec 31, 2005·Molecular and Cellular Biology·Wei ZhangMichael A Weiss
Jul 28, 2009·Annual Review of Genomics and Human Genetics·Melissa A Wilson, Kateryna D Makova
Nov 16, 2013·BMC Genomics·Jeremy W ProkopAmy Milsted
Jul 31, 2013·Oncogene·S MurakamiF Tashiro
Feb 9, 2012·International Journal of Hypertension·Jeremy W ProkopAmy Milsted
Nov 18, 2014·Nature Communications·Wioletta CzajaBruce L Miller
Nov 17, 2009·Steroids·Daniel ElyAmy Milsted

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