DNA replication in eukaryotes is strictly regulated by several mechanisms. A central step in this replication is the assembly of the heterohexameric minichromosome maintenance (MCM2-7) helicase complex at replication origins during G1 phase as an inactive double hexamer. Here, using cryo-electron microscopy, we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin. Our structure shows that two single hexamers, arranged in a tilted and twisted fashion through interdigitated amino-terminal domain interactions, form a kinked central channel. Four constricted rings consisting of conserved interior β-hairpins from the two single hexamers create a narrow passageway that tightly fits duplex DNA. This narrow passageway, reinforced by the offset of the two single hexamers at the double hexamer interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These unusual features of the twisted and tilted single hexamers suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA.
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http://dx.doi.org/10.1038/nature14685 | DOI Listing |
Cell Rep
January 2025
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA. Electronic address:
One of the striking features of human immunodeficiency virus (HIV) is the capsid, a fullerene cone comprised of pleomorphic capsid protein (CA) that shields the viral genome and recruits cofactors. Despite significant advances in understanding the mechanisms of HIV-1 CA assembly and host factor interactions, HIV-2 CA assembly remains poorly understood. By templating the assembly of HIV-2 CA on functionalized liposomes, we report high-resolution structures of the HIV-2 CA lattice, including both CA hexamers and pentamers, alone and with peptides of host phenylalanine-glycine (FG)-motif proteins Nup153 and CPSF6.
View Article and Find Full Text PDFChem Sci
January 2025
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences Fuzhou 350002 China
Traditional tetrahedral-based mid-to-far infrared (MFIR) nonlinear optical (NLO) crystals often face limitations due to the optical anisotropy constraints imposed by their highly symmetric structures. In contrast, the relatively rare trigonal pyramidal [TeS] functional unit characterized by its asymmetric structure and stereochemically active lone pair (SCALP), offers improved optical anisotropy, hyperpolarizability and a broader IR transparency range. Despite its potential, synthetic challenges have hindered the development of MFIR NLO crystals that incorporate this unit, with only one example reported to date.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
is a Gram-positive bacterium that is responsible for severe nosocomial infections. The rise of multidrug-resistant strains, which can pose significant health threats, prompts the development of new treatment interventions, and much attention has been directed at the development of prophylactic and therapeutic vaccination strategies. Capsular polysaccharides (CPs) are key protective elements of the cell wall and have been proposed as promising candidate antigens.
View Article and Find Full Text PDFBiochem J
January 2025
Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
The bacterial transcription terminator Rho is a hexameric ATP-dependent RNA helicase that dislodges elongating RNA polymerases. It has an N-terminal primary RNA binding site (PBS) on each subunit and a C-terminal secondary RNA binding site at the central channel. Here, we show that Rho also binds to linear longer double-stranded DNAs (dsDNA) and the circular plasmids non-specifically using its PBS.
View Article and Find Full Text PDFProtein J
January 2025
Alliance Protein Laboratories, 13380 Pantera Road, San Diego, CA, 92130, USA.
The Ferguson plot is a simple method for determining the molecular weight of native proteins and their complexes. In this study, we tested the validity of the Ferguson plot based on agarose native gel electrophoresis using multimeric chaperone protein, ClpB, derived from a moderate halophile that forms a native hexamer. The Ferguson plot showed a single band with a molecular weight of 1,500 kDa, approximately twice the size of the native hexamer.
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