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Ubiquitination by HECT E3 enzymes regulates myriad processes, including tumor suppression, transcription, protein trafficking, and degradation. HECT E3s use a two-step mechanism to ligate ubiquitin to target proteins. The first step is guided by interactions between the catalytic HECT domain and the E2∼ubiquitin intermediate, which promote formation of a(More)
Imagine two identical people receive exactly the same training on how to classify certain objects. Perhaps surprisingly, we show that one can then manipulate them into classifying some test items in opposite ways, simply depending on what other test items they are asked to classify (without label feedback). We call this the Test-Item Effect, which can be(More)
Recent empirical studies of semi-supervised category learning—where learners only occasionally receive information about a given item's category membership—have yielded contradictory results, with some studies showing strong effects of unlabeled experience and others little or no effect. We report two experiments designed to help understand this(More)
When the distribution of unlabeled data in feature space lies along a manifold, the information it provides may be used by a learner to assist classification in a semi-supervised setting. While manifold learning is well-known in machine learning, the use of manifolds in human learning is largely unstudied. We perform a set of experiments which test a(More)
Mycobacterium tuberculosis places an enormous burden on the welfare of humanity. Its ability to grow and its pathogenicity are linked to sulfur metabolism, which is considered a fertile area for the development of antibiotics, particularly because many of the sulfur acquisition steps in the bacterium are not found in the host. Sulfite reduction is one such(More)
—Humans are adept at identifying informative regions in individual images, but it is a slow and often tedious task to identify the salient parts of every image in a large corpus. A machine, on the other hand, can sift through a large amount of data quickly, but machine methods for identifying salient regions are unreliable. In this paper, we develop a new(More)
The structurally defined ubiquitin-like homology fold (UBL) can engage in several unique protein-protein interactions and many of these complexes have been characterized with high-resolution techniques. Using Rosetta's structural classification tools, we have created the Ubiquitin Structural Relational Database (UbSRD), an SQL database of features for all(More)
Protein ubiquitination involves E1, E2, and E3 trienzyme cascades. E2 and RING E3 enzymes often collaborate to first prime a substrate with a single ubiquitin (UB) and then achieve different forms of polyubiquitination: multiubiquitination of several sites and elongation of linkage-specific UB chains. Here, cryo-EM and biochemistry show that the human E3(More)
The epigenetic inheritance of DNA methylation requires UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that recruits DNMT1 to sites of newly replicated DNA through ubiquitylation of histone H3. UHRF1 binds DNA with selectivity towards hemi-methylated CpGs (HeDNA); however, the contribution of HeDNA sensing to UHRF1 function remains elusive. Here,(More)
Analysis of factors contributing to high affinity antibody-protein interactions provides insight into natural antibody evolution, and guides the design of antibodies with new or enhanced function. We previously studied the interaction between antibody D5 and its target, a designed protein based on HIV-1 gp41 known as 5-Helix, as a model system [Da Silva, G.(More)