Site-directed mutagenesis supports a three-dimensional model of the runt domain

Journal of Molecular Biology
D LevanonY Groner

Abstract

The "runt domain" (RD) is a 128 amino acid region of the Drosophila pair-rule gene runt. This highly conserved region delineates the DNA-binding domain of a new family of transcription factors; the RD proteins. The family includes genes from Drosophila, chicken and mammals that are involved in a wide range of developmental processes, from sex determination and neurogenesis in Drosophila to hematopoiesis and osteoblast differentiation in mouse and human. The RD confers DNA binding ability and mediates the interaction of mammalian RD proteins with the beta-subunit (CBFbeta), which enhances the DNA binding. The primary sequence of RD shows no similarity to other known DNA-binding motifs and its three-dimensional (3D) structure is not known. We employed molecular modeling-based mutagenesis to generate a 3D model of RD. Fold recognition programs identified the palm subdomain of rat DNA polymerase beta as the most likely fold for RD. In the predicted model, the RD region which interacts with DNA contains two arginine residues, R130 and R135, which appear to be in close contact with the major groove of the DNA and to interact with the three essential guanine bases of the core DNA motif PyGPyGGT. We mutated these two R residues and dem...Continue Reading

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Citations

Apr 2, 1999·European Journal of Biochemistry·M Wolf-WatzT Härd
Nov 6, 2002·Orthodontics & Craniofacial Research·I GolanD Müssig
Aug 16, 2014·Cell Research·Zhimin Lu, Tony Hunter
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Feb 14, 2020·Viruses·Weam ElbezantiZachary Klase
Nov 2, 2021·Frontiers in Oncology·Wenwen ZhangMinyi Zhao

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