12 December, 2008
Volume 16, Issue 12

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Volume 16, Issue 12

On the cover: DNA replication is carried out by multiprotein machines that unwind the parental DNA double-helix (spooling in at left) and synthesize new daughter strands from each single-stranded template (emerging at the right). The assembly of these machines on DNA and the mechanisms by which they coordinate DNA unwinding and synthesis remain somewhat of a black box in eukaryotic organisms. The Mcm10 protein is an integral component of the eukaryotic replisome through its interactions with single- and double-stranded DNA as well as key proteins at the replication fork. The crystal structure of Mcm10's DNA binding domain (see Warren et al., pp. 1892–1901), shown in green and blue inside the replication machine, reveals how the protein utilizes a unique arrangement of DNA binding elements to interact with a single DNA strand, depicted here as a gold ribbon. The structure represents a high-resolution glimpse into a core component of the eukaryotic replication complex and provides important insight into the manner in which Mcm10 might interact with the other proteins involved in DNA replication. (Cover artwork created by Jessica Eichman and Glass Egg Graphic Design).

Annotated Table
of Contents


Most Read Papers

  • These are the Top 20 Papers by download from the Structure web site for the last 30 days.


Recently Described Tools

The following are recently described tools for structural biologists

Accurate NMR Structures Through Minimization of an Extended Hybrid Energy
Michael Nilges, Aymeric Bernard, Benjamin Bardiaux, Therese Malliavin, Michael Habeck and Wolfgang Rieping
Structure 16(9), 1305
A Lipidic-Sponge Phase Screen for Membrane Protein Crystallization
Annemarie B. Wohri, Linda C. Johansson, Pia Wadsten-Hindrichsen, Weixiao Y. Wahlgren, Gerhard Fischer, Rob Horsefield, Gergely Katona, Maria Nyblom, Fredrik Oberg, Gillian Young, Richard J. Cogdell, Niall J. Fraser, Sven Engstrom, and Richard Neutze
Structure 16(7), 1003
Preparation of Multimilligram Quantities of Large, Linear DNA Molecules for Structural Studies
Merlind Muecke, Martin Samuels, Megan Davey, and David Jeruzalmi
Structure 16(6), 837
Flexible Fitting of Atomic Structures into Electron Microscopy Maps Using Molecular Dynamics
Leonardo G. Trabuco, Elizabeth Villa, Kakoli Mitra, Joachim Frank, and Klaus Schulten
Structure 16(5), 673
Microscale Fluorescent Thermal Stability Assay for Membrane Proteins
Alexander I. Alexandrov, Mauro Mileni, Ellen Y.T. Chien, Michael A. Hanson, and Raymond C. Stevens
Structure 16 (3), 351

Current Issue

Volume 16 Issue 12: December 10, 2008

Next issue: January 14, 2009

Included in this issue

  • Ways & Means: 'Hypothetical Proteins' - Busted!
  • Ways & Means: Chemical Shifts Tell it All
  • Technical Advance: 3D Cryo-EM Variance Analysis to Tackle Heterogeneity
  • Predicting Sequence at a Protein-Protein Interface
  • Extensive Negative Design Not Required
  • Cryptic FHA Domain of Pellino
  • Disordered Phosphorylation Loops in PDC
  • Snapshots of Catalysis in PDC
  • Villin not Villain
  • Cover Story: Churning the DNA
  • Click here for the complete table of contents.

    Featured Article

    The Featured Articles are freely available to all readers.

    Pellino proteins contain a cryptic FHA domain that mediates interaction with phosphorylated IRAK1

    Chun-Chi Lin, Yu-San Huoh, Karl R. Schmitz, Liselotte E. Jensen and Kathryn M. Ferguson

    Lin et al identify the molecular basis of substrate recognition by the RING E3 ubiquitin ligase Pellino. They report the crystal structure of the substrate-binding region of Pellino2 that unexpectedly comprises entirely of a non-canonical forkhead-associated (FHA) domain. FHA domains are well-characterized phosphothreonine-binding modules, and observation of this domain in Pellino2 provides a molecular framework to understand the mechanism, and regulation, of substrate recognition by this E3 ligase. The Pellino FHA core has all the conserved features required for phosphothreonine binding and is also decorated by an unusual wing-like appendage that may also participate in substrate recognition. (Figure modified from Lin et al.)

    In this Issue

    Deng V-ATPase Regulation by Reversible Dissociation
    Vacuolar ATPases are membrane-integrated ATP-dependent proton pumps that acidify intracellular compartments and the extracellular space. The unique regulatory mode of this enzyme by reversible assembly/disassembly is related to the topological arrangement of its peripheral subunits. Diepholz et al. now reveal differences in the conformation of the EGC stator sub-complex that may have some functional significance during regulatory assembly/disassembly.
    Bhatt GFP-calmodulin Sensor Shining Bright
    In addition to their role as a visible tag, Green Fluorescent Proteins (GFPs) have been linked to receptor peptides that regulate fluorescence in a state-dependent fashion. Wang et al. report the molecular mechanism of the Ca2+-dependent fluorescence of GCaMP2, a GFP-calmodulin sensor that reports rapid changes in Ca2+ in living cells.
    Anzai Sensing the DNA Sequence
    Sequence specific DNA binding proteins must find their target site rapidly in a vast sea of non-target sequences. Recognition of DNA sequences can occur through direct readout, with direct contacts to the DNA bases, or possibly also by indirect readout, where sequences are "sensed" through the energetics of DNA distortion. Little et al. show that a mutant enzyme missing direct readout contacts retained full target site selectivity, demonstrating the significance of indirect readout.
    Levy Pilus Fiber Biogenesis Busted!
    Streptococcus pneumoniae contains, on its surface, pili, hair-like, elongated fibers that are involved in pathogenicity. The machinery for pilus formation encodes seven genes, three for structural proteins (RrgA, RrgB, and RrgC) and three for sortases (SrtC-1, SrtC-2, SrtC-3). Now, Manzano et al. show that SrtC-1 is the main RrgB fiber-forming transpeptidase, both in vitro and in vivo.
    Levy YaeT PD: Importance of Being Flexible
    Outer membrane proteins (OMPs) of Gram-negative bacteria are synthesized in cytoplasm and subsequently transported through inner membrane and the periplasm and delivered to outer membrane (OM). The mechanism of OMPs targeting and insertion into OM is not well-understood. Here, Gatzeva-Topalova et al. investigate periplasmic domain (PD) of bacterial Omp85 protein from E. coli, YeaT, required for large number of OMP insertion.