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Crystal Structure Of A Near Full-Length Archaeal MCM: Functional Insights For An AAA+ Hexameric Helicase
Structural highlights
FunctionMCM_SACS2 Presumptive replicative helicase. Has ATPase and DNA helicase activities. The latter preferentially melts 5'-tailed oligonucleotides and is stimulated by the SSB protein (single-stranded DNA binding protein). The active ATPase sites in the MCM ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The helicase function is proposed to use a partially sequential mode of ATP hydrolysis; the complex appears to tolerate multiple catalytically inactive subunits.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe minichromosome maintenance protein (MCM) complex is an essential replicative helicase for DNA replication in Archaea and Eukaryotes. Whereas the eukaryotic complex consists of 6 homologous proteins (MCM2-7), the archaeon Sulfolobus solfataricus has only 1 MCM protein (ssoMCM), 6 subunits of which form a homohexamer. Here, we report a 4.35-A crystal structure of the near-full-length ssoMCM. The structure shows an elongated fold, with 5 subdomains that are organized into 2 large N- and C-terminal domains. A near-full-length ssoMCM hexamer generated based on the 6-fold symmetry of the N-terminal Methanothermobacter thermautotrophicus (mtMCM) hexamer shows intersubunit distances suitable for bonding contacts, including the interface around the ATP pocket. Four unusual beta-hairpins of each subunit are located inside the central channel or around the side channels in the hexamer. Additionally, the hexamer fits well into the double-hexamer EM map of mtMCM. Our mutational analysis of residues at the intersubunit interfaces and around the side channels demonstrates their critical roles for hexamerization and helicase function. These structural and biochemical results provide a basis for future study of the helicase mechanisms of the archaeal and eukaryotic MCM complexes in DNA replication. Crystal structure of a near-full-length archaeal MCM: Functional insights for an AAA+ hexameric helicase.,Brewster AS, Wang G, Yu X, Greenleaf WB, Carazo JM, Tjajadia M, Klein MG, Chen XS Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20191-6. Epub 2008 Dec 10. PMID:19073923[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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