Theme B Highlights
Theme B Proteins involved in or suspected to be involved DNA binding and manipulation, mainly from Sulfolobus solfataricus.
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| Hel308 is a superfamily 2 helicase conserved in eukaryotes and archaea. It is thought to function in the early stages of recombination following replication fork arrest, and has a specificity for removal of the lagging strand in model replication forks. A homologous helicase constitutes the N-terminal domain of human DNA polymerase Q. The Drosophila homologue mus301 is implicated in double strand break repair and meiotic recombination. We have solved the high-resolution crystal structure of Hel308 from the crenarchaeon Sulfolobus solfataricus, revealing a five-domain structure with a central pore lined with essential DNA binding residues. The fifth domain is shown to act as a molecular brake, clamping the ssDNA extruded through the central pore of the helicase structure to limit the enzyme’s helicase activity. At over 700 residues this is substantial undertaking.
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| SSoXPD4 This is a novel helicase, with a close counterpart in human and contains a unique FeS regulatory domain. The full length protein is over 500 amino acids. We have determined the structure of the apo (non FeS) protein and can now interpret several mutations linked to human disease. The redox status of the FeS domain is crucial to activity. We have small promising crystal of protein with intact FeS domains.
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| Sso2273 is a transcriptional repressor of the diptheria toxin repressor (DtxR) family. The protein has been identified as a metal-dependent repressor of the Dps protein in Sulfolobus solfataricus in the White lab. Dps is involved in the detoxification of reactive oxygen species such as hydrogen peroxide. The structure of Sso2273 reveals a dimeric molecule where each monomer has 2 domains: an N-terminal domain with two bound Zn ions, and a C-terminal DNA binding domain. Conformational changes on metal ion binding result in re-positioning of the DNA binding domains and determine gene expression patterns.
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| Sso1404 is a member of the CRISPR-associated or CAS protein family, with the designation CAS2. CRISPRs are clusters of short repeat elements found in many prokaryotic genomes, often of viral origin. They are thought to represent some form of primitive immunity system similar to RNAi in eukaryotes. The function of the CAS proteins is thought to be in the processing of the CRISPR sequences and the antiviral function, although none of these proteins has a clearly defined role. This is one of the first reported structures of a CAS protein. It reveals a dimeric structure with conserved residues occupying a central groove, suggesting a binding surface for DNA or RNA. Biochemical studies to characterise the function of the protein are currently underway.
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| Sso2452 is a RadA paralogue and a member of the RecA superfamily of DNA recombinases. In addition to RadA, the primary archaeal recombinase, most crenarchaea have one or more RadA paralogues whose function is unknown. This is the first reported structure of a crenarchaeal RadA paralogue. The fold resembles the core ATP binding domain of the RecA superfamily. Extensive biochemical data is available for this protein, which will be published along with the structure.
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©Scottish Structural Proteomics Facility 2007.
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Updated:30-10-07 |
