RESUMO
The sigma subunit of eubacterial RNA polymerase is required throughout initiation, but how it communicates with core polymerase (alpha(2)betabeta') is poorly understood. The present work addresses the location and function of the interface of sigma with core. Our studies suggest that this interface is extensive as mutations in six conserved regions of sigma(70) hinder the ability of sigma to bind core. Direct binding of one of these regions to core can be demonstrated using a peptide-based approach. The same regions, and even equivalent residues, in sigma(32) and sigma(70) alter core interaction, suggesting that sigma(70) family members use homologous residues, at least in part, to interact with core. Finally, the regions of sigma that we identify perform specialized functions, suggesting that different portions of the interface perform discrete roles during transcription initiation.
Assuntos
Proteínas de Bactérias/química , RNA Polimerases Dirigidas por DNA/química , Proteínas de Choque Térmico/química , RNA Polimerase I/química , Fator sigma/química , Fatores de Transcrição/química , Transcrição Gênica , Sequência de Aminoácidos , Substituição de Aminoácidos , Proteínas de Bactérias/metabolismo , Sítios de Ligação , RNA Polimerases Dirigidas por DNA/genética , RNA Polimerases Dirigidas por DNA/metabolismo , Escherichia coli/enzimologia , Escherichia coli/genética , Proteínas de Choque Térmico/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , RNA Polimerase I/metabolismo , Proteínas Recombinantes de Fusão/química , Fator sigma/genética , Fator sigma/metabolismo , Fatores de Transcrição/metabolismoRESUMO
The cutaneous penetration of acyclovir can be significantly increased from a propylene glycol base vehicle by adding small amounts of a polar lipid such as oleic acid. These results are consistent with those found for salicylic acid, and the large increases in acyclovir penetration could potentially lead to better topical treatment of herpes simplex.