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We describe tethered conformation capture (TCC), a method for genome-wide mapping of chromatin interactions. By performing ligations on solid substrates rather than in solution, TCC substantially enhances the signal-to-noise ratio, thereby facilitating a detailed analysis of interactions within and between chromosomes. We identified a group of regions in(More)
Nuclear pore complexes (NPCs) are proteinaceous assemblies of approximately 50 MDa that selectively transport cargoes across the nuclear envelope. To determine the molecular architecture of the yeast NPC, we collected a diverse set of biophysical and proteomic data, and developed a method for using these data to localize the NPC's 456 constituent proteins(More)
To understand the workings of a living cell, we need to know the architectures of its macromolecular assemblies. Here we show how proteomic data can be used to determine such structures. The process involves the collection of sufficient and diverse high-quality data, translation of these data into spatial restraints, and an optimization that uses the(More)
The nuclear pore complex (NPC) consists of multiple copies of approximately 30 different proteins [nucleoporins (nups)], forming a channel in the nuclear envelope that mediates macromolecular transport between the cytosol and the nucleus. With <5% of the nup residues currently available in experimentally determined structures, little is known about the(More)
Numerous features distinguish prokaryotes from eukaryotes, chief among which are the distinctive internal membrane systems of eukaryotic cells. These membrane systems form elaborate compartments and vesicular trafficking pathways, and sequester the chromatin within the nuclear envelope. The nuclear pore complex is the portal that specifically mediates(More)
Structures of macromolecular complexes are necessary for a mechanistic description of biochemical and cellular processes. They can be solved by experimental methods, such as X-ray crystallography, NMR spectroscopy and electron microscopy, as well as by computational protein structure prediction, docking and bioinformatics. Recent advances and applications(More)
We describe comparative patch analysis for modeling the structures of multidomain proteins and protein complexes, and apply it to the PSD-95 protein. Comparative patch analysis is a hybrid of comparative modeling based on a template complex and protein docking, with a greater applicability than comparative modeling and a higher accuracy than docking. It(More)
In this paper we show that tethering of heterochromatic regions to nuclear landmarks and random encounters of chromosomes in the confined nuclear volume are sufficient to explain the higher-order organization of the budding yeast genome. We have quantitatively characterized the contact patterns and nuclear territories that emerge when chromosomes are(More)
To understand the cell, we need to determine the macromolecular assembly structures, which may consist of tens to hundreds of components. First, we review the varied experimental data that characterize the assemblies at several levels of resolution. We then describe computational methods for generating the structures using these data. To maximize(More)
We suggest structure characterization of macromolecular assemblies by combining assembly shape determined by electron cyromicroscopy with information about subunit proximity determined by affinity purification. To achieve this aim, structure characterization is expressed as a problem in satisfaction of spatial restraints that (1) represents subunits as(More)