Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins.

Niemann-Pick type C (NPC) proteins are essential for sterol homeostasis, believed to drive sterol integration into the lysosomal membrane before redistribution to other cellular membranes. Here, using a combination of crystallography, cryo-electron microscopy, and biochemical and in vivo studies on the Saccharomyces cerevisiae NPC system (NCR1 and NPC2), we present a framework for sterol membrane integration. Sterols are transferred between hydrophobic pockets of vacuolar NPC2 and membrane-protein NCR1.

- automatic molecular dynamics flexible fitting of structural models into cryo-EM and crystallography experimental maps.

Model building into experimental maps is a key element of structural biology, but can be both time consuming and error prone for low-resolution maps. Here we present , an easy-to-use tool that enables the user to run a molecular dynamics flexible fitting simulation followed by real-space refinement in an automated manner through a pipeline system. will modify an atomic model to fit within cryo-EM or crystallography density maps, and can be used advantageously for both the initial fitting of models, and for a geometrical optimization step to correct outliers, clashes and other model problems.

Interacting with the Human Insulin Receptor.

Insulin is an essential regulator of glucose homeostasis. In this issue of Structure, Croll et al. (2016) reports a significantly improved model of the Fab-complexed IR ectodomain refined against a dataset extending to 3.

Structure of TSA2 reveals novel features of the active-site loop of peroxiredoxins.

Saccharomyces cerevisiae TSA2 belongs to the family of typical 2-Cys peroxiredoxins, a ubiquitously expressed family of redox-active enzymes that utilize a conserved peroxidatic cysteine to reduce peroxides. Typical 2-Cys peroxiredoxins have been shown to be involved in protection against oxidative stress and in hydrogen peroxide signalling. Furthermore, several 2-Cys peroxiredoxins, including S.

Structural Basis for the Function of Complement Component C4 within the Classical and Lectin Pathways of Complement.

Complement component C4 is a central protein in the classical and lectin pathways within the complement system. During activation of complement, its major fragment C4b becomes covalently attached to the surface of pathogens and altered self-tissue, where it acts as an opsonin marking the surface for removal. Moreover, C4b provides a platform for assembly of the proteolytically active convertases that mediate downstream complement activation by cleavage of C3 and C5.

Structural basis for activation of the complement system by component C4 cleavage.

An essential aspect of innate immunity is recognition of molecular patterns on the surface of pathogens or altered self through the lectin and classical pathways, two of the three well-established activation pathways of the complement system. This recognition causes activation of the MASP-2 or the C1s serine proteases followed by cleavage of the protein C4. Here we present the crystal structures of the 203-kDa human C4 and the 245-kDa C4·MASP-2 substrate·enzyme complex.

Structure of the Qbeta replicase, an RNA-dependent RNA polymerase consisting of viral and host proteins.

The RNA-dependent RNA polymerase core complex formed upon infection of Escherichia coli by the bacteriophage Qbeta is composed of the viral catalytic beta-subunit as well as the host translation elongation factors EF-Tu and EF-Ts, which are required for initiation of RNA replication. We have determined the crystal structure of the complex between the beta-subunit and the two host proteins to 2.5-A resolution.