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  1. Free, publicly-accessible full text available January 21, 2023
  2. Abstract. Recent research on fold-switching metamorphic proteins has revealed some notable exceptions to Anfinsen's hypothesis of protein folding. We have previously described how a single point mutation can enable a well-folded protein domain, one of the two PAS (Per-ARNT-Sim) domains of the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein, to interconvert between two conformers related by a slip of an internal β strand. Using this protein as a test case, we advance the concept of a “fragile fold”, a protein fold that can reversibly rearrange into another fold that differs by a substantial number of hydrogen bonds, entailing reorganization of single secondary structure elements to more drastic changes seen in metamorphic proteins. Here we use a battery of biophysical tests to examine several factors affecting the equilibrium between the two conformations of the switching ARNT PAS-B Y456T protein. Of note is that we find that factors which impact the HI loop preceding the shifted Iβ strand affect both the equilibrium levels of the two conformers and the denatured state which links them in the interconversion process. Finally, we describe small molecules that selectively bind to and stabilize the wild-type conformation of ARNT PAS-B. These studies form a toolkit for studying fragile proteinmore »folds and could enable ways to modulate the biological functions of such fragile folds, both in natural and engineered proteins.« less
  3. The need to train sustainability scientists and engineers to address the complex problems of our world has never been more apparent. We organized an interdisciplinary team of instructors from universities in the states of Maine, New Hampshire, and Rhode Island who designed, taught, and assessed a multi-university course to develop the core competencies necessary for advancing sustainability solutions. Lessons from the course translate across sustainability contexts, but our specific focus was on the issues and trade-offs associated with dams. Dams provide numerous water, energy, and cultural services to society while exacting an ecological toll that disrupts the flow of water, fish, and sediment in rivers. Like many natural resource management challenges, effective dam decisions require collaboration among diverse stakeholders and disciplines. We linked key sustainability principles and practices related to interdisciplinarity, stakeholder engagement, and problem-solving to student learning outcomes that are generalizable beyond our dam-specific context. Students and instructors co-created class activities to build capacity for interdisciplinary collaboration and encourage student leadership and creativity. Assessment results show that students responded positively to activities related to stakeholder engagement and interdisciplinary collaboration, particularly when practicing nested discussion and intrapersonal reflection. These activities helped broaden students’ perspectives on sustainability problems and built greatermore »capacity for constructive communication and student leadership.« less