Drosophila IAP antagonists form multimeric complexes to promote cell death

Self- and hetero-association of the pro-apoptotic proteins Reaper, Hid, and Grim is required for efficient induction of the cell death program

Mobile writing technologies and the dis /location of the computer classroom

This dissertation conceptualizes the wireless writing classroom as a nexus where administrators\u27, instructors\u27, and students\u27 desires are often at odds with each other. Bringing these competing desires to the fore, this work highlights the fissures that tend to get paved over by time and power, fissures that, when exposed and interrogated, represent opportunities for institutional change accomplished via rhetoric. The project problematizes the manner in which some scholars (fail to) conceptualize place and in turn fosters a plastic view of place as unfixed intersection that defies simple, firm enclosures. Drawing from technical and professional writing, rhetoric and composition, human-computer interaction, and other fields, the present study argues for a more participatory approach to wireless design that takes stakeholders\u27 favored spatial arrangements and names for wireless classrooms into account. It culminates in a series of comprehensive design heuristics that accommodate competing discourses and preferences

1H, 13C, 15N resonance assignments and secondary structure of yeast oligosaccharyltransferase subunit Ost4 and its functionally important mutant Ost4V23D

Asparagine-linked glycosylation is an essential and highly conserved protein modification reaction that occurs in the endoplasmic reticulum of cells during protein synthesis at the ribosome. In the central reaction, a pre-assembled high-mannose sugar is transferred from a lipid-linked donor substrate to the side-chain of an asparagine residue in an -N-X-T/S- sequence (where X is any residue except proline). This reaction is carried by a membrane-bound multi-subunit enzyme complex, oligosaccharyltransferase (OST). In humans, genetic defects in OST lead to a group of rare metabolic diseases collectively known as Congenital Disorders of Glycosylation. Certain mutations are lethal for all organisms. In yeast, the OST is composed of nine non-identical protein subunits. The functional enzyme complex contains eight subunits with either Ost3 or Ost6 at any given time. Ost4, an unusually small protein, plays a very important role in the stabilization of the OST complex. It bridges the catalytic subunit Stt3 with Ost3 (or Ost6) in the Stt3-Ost4-Ost3 (or Ost6) sub-complex. Mutation of any residue from M18-I24 in the trans-membrane helix of yeast Ost4 negatively impacts N-linked glycosylation and the growth of yeast. Indeed, mutation of valine23 to an aspartate impairs OST function in vivo resulting in a lethal phenotype in yeast. To understand the structural mechanism of Ost4 in the stabilization of the enzyme complex, we have initiated a detailed investigation of Ost4 and its functionally important mutant, Ost4V23D. Here, we report the backbone 1H, 13C, and 15N resonance assignments for Ost4 and Ost4V23D in dodecylphosphocholine micelles

Structural Insight into the Mechanism of N-Linked Glycosylation by Oligosaccharyltransferase

Asparagine-linked glycosylation, also known as N-linked glycosylation is an essential and highly conserved post-translational protein modification that occurs in all three domains of life. This modification is essential for specific molecular recognition, protein folding, sorting in the endoplasmic reticulum, cell–cell communication, and stability. Defects in N-linked glycosylation results in a class of inherited diseases known as congenital disorders of glycosylation (CDG). N-linked glycosylation occurs in the endoplasmic reticulum (ER) lumen by a membrane associated enzyme complex called the oligosaccharyltransferase (OST). In the central step of this reaction, an oligosaccharide group is transferred from a lipid-linked dolichol pyrophosphate donor to the acceptor substrate, the side chain of a specific asparagine residue of a newly synthesized protein. The prokaryotic OST enzyme consists of a single polypeptide chain, also known as single subunit OST or ssOST. In contrast, the eukaryotic OST is a complex of multiple non-identical subunits. In this review, we will discuss the biochemical and structural characterization of the prokaryotic, yeast, and mammalian OST enzymes. This review explains the most recent high-resolution structures of OST determined thus far and the mechanistic implication of N-linked glycosylation throughout all domains of life. It has been shown that the ssOST enzyme, AglB protein of the archaeon Archaeoglobus fulgidus, and the PglB protein of the bacterium Campylobactor lari are structurally and functionally similar to the catalytic Stt3 subunit of the eukaryotic OST enzyme complex. Yeast OST enzyme complex contains a single Stt3 subunit, whereas the human OST complex is formed with either STT3A or STT3B, two paralogues of Stt3. Both human OST complexes, OST-A (with STT3A) and OST-B (containing STT3B), are involved in the N-linked glycosylation of proteins in the ER. The cryo-EM structures of both human OST-A and OST-B complexes were reported recently. An acceptor peptide and a donor substrate (dolichylphosphate) were observed to be bound to the OST-B complex whereas only dolichylphosphate was bound to the OST-A complex suggesting disparate affinities of two OST complexes for the acceptor substrates. However, we still lack an understanding of the independent role of each eukaryotic OST subunit in N-linked glycosylation or in the stabilization of the enzyme complex. Discerning the role of each subunit through structure and function studies will potentially reveal the mechanistic details of N-linked glycosylation in higher organisms. Thus, getting an insight into the requirement of multiple non-identical subunits in the N-linked glycosylation process in eukaryotes poses an important future goal

User-centered technology in participatory culture: Two decades Beyond a narrow conception of usability testing

Twenty years after the publication of Patricia Sullivan\u27s Beyond a narrow conception of usability testing in the IEEE Transactions on Professional Communication, three scholars-all Sullivan\u27s students-reflect on the history and development of usability testing and research. Following Sullivan, this article argues that usability bridges the divide between science and rhetoric and asserts that usability is most effective when it respects the knowledge-making practices of a variety of disciplines. By interrogating trends in usability method, the authors argue for a definition of usability that relies on multiple epistemologies to triangulate knowledge-making. The article opens with a brief history of the development of usability methods and argues that usability requires a balance between empirical observation and rhetoric. Usability interprets human action and is enriched by articulating context and accepting contingency. Usability relies on effective collaboration and cooperation among stakeholders in the design of technology. Ultimately, professional and technical communication scholars are best prepared to coin new knowledge with a long and wide view of usability. © 2007 IEEE