3,999 research outputs found
Software Extensions to UCSF Chimera for Interactive Visualization of Large Molecular Assemblies
SummaryMany structures of large molecular assemblies such as virus capsids and ribosomes have been experimentally determined to atomic resolution. We consider four software problems that arise in interactive visualization and analysis of large assemblies: how to represent multimers efficiently, how to make cartoon representations, how to calculate contacts efficiently, and how to select subassemblies. We describe techniques and algorithms we have developed and give examples of their use. Existing molecular visualization programs work well for single protein and nucleic acid molecules and for small complexes. The methods presented here are proposed as features to add to existing programs or include in next-generation visualization software to allow easy exploration of assemblies containing tens to thousands of macromolecules. Our approach is pragmatic, emphasizing simplicity of code, reliability, and speed. The methods described have been distributed as the Multiscale extension of the UCSF Chimera (www.cgl.ucsf.edu/chimera) molecular graphics program
University science students as curriculum planners, teachers, and role models in elementary school classrooms
Tools for integrated sequence-structure analysis with UCSF Chimera
BACKGROUND: Comparing related structures and viewing the structures in the context of sequence alignments are important tasks in protein structure-function research. While many programs exist for individual aspects of such work, there is a need for interactive visualization tools that: (a) provide a deep integration of sequence and structure, far beyond mapping where a sequence region falls in the structure and vice versa; (b) facilitate changing data of one type based on the other (for example, using only sequence-conserved residues to match structures, or adjusting a sequence alignment based on spatial fit); (c) can be used with a researcher's own data, including arbitrary sequence alignments and annotations, closely or distantly related sets of proteins, etc.; and (d) interoperate with each other and with a full complement of molecular graphics features. We describe enhancements to UCSF Chimera to achieve these goals. RESULTS: The molecular graphics program UCSF Chimera includes a suite of tools for interactive analyses of sequences and structures. Structures automatically associate with sequences in imported alignments, allowing many kinds of crosstalk. A novel method is provided to superimpose structures in the absence of a pre-existing sequence alignment. The method uses both sequence and secondary structure, and can match even structures with very low sequence identity. Another tool constructs structure-based sequence alignments from superpositions of two or more proteins. Chimera is designed to be extensible, and mechanisms for incorporating user-specific data without Chimera code development are also provided. CONCLUSION: The tools described here apply to many problems involving comparison and analysis of protein structures and their sequences. Chimera includes complete documentation and is intended for use by a wide range of scientists, not just those in the computational disciplines. UCSF Chimera is free for non-commercial use and is available for Microsoft Windows, Apple Mac OS X, Linux, and other platforms from
Activation of the Wnt Signaling Pathway: A Molecular Mechanism for Lithium Action
AbstractGlycogen synthase kinase-3β (GSK-3β/zeste-white-3/shaggy) is a negative regulator of the wnt signaling pathway which plays a central role in the development of invertebrates and vertebrates; loss of function and dominant negative mutations in GSK-3β lead to activation of the wnt pathway inDrosophilaandXenopus.We now provide evidence that lithium activates downstream components of the wnt signaling pathwayin vivo,leading to accumulation of β-catenin protein. Our data indicate that this activation of the wnt pathway is a consequence of inhibition of GSK-3β by lithium. Using a novel assay for GSK-3β in oocytes, we show that lithium inhibits GSK-3β from species as diverse asDictyostelium discoideumandXenopus laevis,providing a biochemical mechanism for the action of lithium on the development of these organisms. Lithium treatment also leads to activation of an AP-1–luciferase reporter inXenopusembryos, consistent with previous observations that GSK-3β inhibits c-jun activity. Activation of the wnt pathway with a dominant negative form of GSK-3β is inhibited by myo-inositol, similar to the previously described effect of coinjecting myo-inositol with lithium. The mechanism by which myo-inositol inhibits both dominant negative GSK-3β and lithium remains uncertain
Control of electron transport routes through redox-regulated redistribution of respiratory complexes
Hemojuvelin-Neogenin Interaction Is Required for Bone Morphogenic Protein-4-induced Hepcidin Expression
Hemojuvelin (HJV) is a glycosylphosphatidylinositol-linked protein and binds both bone morphogenic proteins (BMPs) and neogenin. Cellular HJV acts as a BMP co-receptor to enhance the transcription of hepcidin, a key iron regulatory hormone secreted predominantly by liver hepatocytes. In this study we characterized the role of neogenin in HJV-regulated hepcidin expression. Both HJV and neogenin were expressed in liver hepatocytes. Knockdown of neogenin decreased BMP4-induced hepcidin mRNA levels by 16-fold in HJV-expressing HepG2 cells but only by about 2-fold in cells transfected with either empty vector or G99V mutant HJV that does not bind BMPs. Further studies indicated that disruption of the HJV-neogenin interaction is responsible for a marked suppression of hepcidin expression. Moreover, in vivo studies showed that hepatic hepcidin mRNA could be significantly suppressed by blocking the interaction of HJV with full-length neogenin with a soluble fragment of neogenin in mice. Together, these results suggest that the HJV-neogenin interaction is required for the BMP-mediated induction of hepcidin expression when HJV is expressed. Combined with our previous studies, our results support that hepatic neogenin possesses two functions, mediation of cellular HJV release, and stimulation of HJV-enhanced hepcidin expression
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