The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/.

/pdf/ucsf-chimera-a-visualization-system-for-exploratory-research-59xu54fhxg.pdf

UCSF Chimera--a visualization system for exploratory research and analysis.

EMAN2: an extensible image processing suite for electron microscopy.

EMAN: semiautomated software for high-resolution single-particle reconstructions.

The N-terminal domains of gasdermin proteins cause pyroptotic cell death by oligomerizing to form membrane pores.

Pore-forming activity and structural autoinhibition of the gasdermin family

Transient receptor potential (TRP) channels are sensors for a wide range of cellular and environmental signals, but elucidating how these channels respond to physical and chemical stimuli has been hampered by a lack of detailed structural information. Here we exploit advances in electron cryo-microscopy to determine the structure of a mammalian TRP channel, TRPV1, at 3.4 A resolution, breaking the side-chain resolution barrier for membrane proteins without crystallization. Like voltage-gated channels, TRPV1 exhibits four-fold symmetry around a central ion pathway formed by transmembrane segments 5–6 (S5–S6) and the intervening pore loop, which is flanked by S1–S4 voltage-sensor-like domains. TRPV1 has a wide extracellular ‘mouth’ with a short selectivity filter. The conserved ‘TRP domain’ interacts with the S4–S5 linker, consistent with its contribution to allosteric modulation. Subunit organization is facilitated by interactions among cytoplasmic domains, including amino-terminal ankyrin repeats. These observations provide a structural blueprint for understanding unique aspects of TRP channel function. A high-resolution electron cryo-microscopy structure of the rat transient receptor potential (TRP) channel TRPV1 in its ‘closed’ state is presented; the overall structure of this ion channel is found to share some common features with voltage-gated ion channels, although several unique, TRP-specific features are also characterized. Transient receptor potential (TRP) channels are sensors for a wide range of physical and chemical stimuli. In the first of a pair of related papers, Maofu Liao et al. solve the high-resolution electron cryo-microscopy structure of rat TRPV1, the receptor for capsaicin (a pungent agent from chili peppers), in a 'closed' state. The overall structure is fairly similar to that of a voltage-gated ion channel, but there are several structural features unique to TRP channels. In the second paper, Erhu Cao et al. present the structures of rat TRPV1 in the presence of a peptide neurotoxin (resiniferatoxin) and in the presence of capsaicin, yielding structures of activated states of the channel. Comparison of the closed and open structures suggests that TRPV1 has a unique two-gate mechanism of channel activation.

/pdf/structure-of-the-trpv1-ion-channel-determined-by-electron-2xjl0arkny.pdf

Mahieddine Ladjadj

Papers

Spider and web : processing and visualization of images in 3d electron microscopy and related fields