STRUCTURAL HOMOLOGY BETWEEN THE RAP30 DNA-BINDING DOMAIN AND LINKER HISTONE H5 - IMPLICATIONS FOR PREINITIATION COMPLEX ASSEMBLY

The three-dimensional structure of the human Rap30 DNA-binding domain has been solved by multinuclear NMR spectroscopy. The structure of the globular domain is strikingly similar to that of linker histone H5 an d its fold places Rap30 into the ''winged'' helix-turn-helix family of eukaryotic transcription factors, Although the domain interacts weakl y with DNA, the binding surface was identified and shown to be consist ent with the structure of the HNF-3/fork head-DNA complex. The archite cture of the Rap30 DNA-binding domain has important implications for t he function of Rap30 in the assembly of the preinitiation complex. In analogy to the function of linker histones in chromatin formation, the fold of the Rap30 DNA-binding domain suggests that its role in transc ription initiation may be that of a condensation factor for preinitiat ion complex assembly. Functional similarity to linker histones may exp lain the dependence of Rap30 binding on the bent DNA environment induc ed by the TATA box-binding protein. Cryptic sequence identity and func tional homology between the Rap30 DNA-binding domain and region 4 of E scherichia coli sigma(70) may indicate that the sigma factors also pos sess a linker histone-like activity in the formation of a prokaryotic closed complex.