title: Crystal structure of the SF3 helicase from adeno-associated virus type 2.
abstract: We report here the crystal structure of an SF3 DNA helicase, Rep40, from adeno-associated virus 2 (AAV2). We show that AAV2 Rep40 is structurally more similar to the AAA(+) class of cellular proteins than to DNA helicases from other superfamilies. The structure delineates the expected Walker A and B motifs, but also reveals an unexpected "arginine finger" that directly implies the requirement of Rep40 oligomerization for ATP hydrolysis and helicase activity. Further, the Rep40 AAA(+) domain is novel in that it is unimodular as opposed to bimodular. Altogether, the structural connection to AAA(+) proteins defines the general architecture of SF3 DNA helicases, a family that includes simian virus 40 (SV40) T antigen, as well as provides a conceptual framework for understanding the role of Rep proteins during AAV DNA replication, packaging, and site-specific integration.
authors.affiliation: Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: J Anson
authors.initials: JA
authors.lastname: James
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Escalante
authors.forename: Miran
authors.initials: M
authors.lastname: Yoon-Robarts
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Edwards
authors.forename: R Michael
authors.initials: RM
authors.lastname: Linden
authors.forename: Aneel K
authors.initials: AK
authors.lastname: Aggarwal
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D004265:DNA Helicases / Q000737:chemistry*; D000229:Dependovirus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology; D015870:Gene Expression; D006193:Haemophilus influenzae / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D016963:Thermus thermophilus / Q000201:enzymology; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D004265:DNA Helicases