Venomous animals immobilize prey using protein toxins that act on ion channels and other targets of biological importance. Broad use of toxins for biomedical research, diagnosis, and therapy has been limited by inadequate target discrimination, for example, among ion channel subtypes. Here, a synthetic toxin is produced by a new strategy to be specific for human Kv1.3 channels, critical regulators of immune T cells. A phage display library of 11,200 de novo proteins is designed using the ␣-KTx scaffold of 31 scorpion toxin sequences known or predicted to bind to potassium channels. Mokatoxin-1 (moka1) is isolated by affinity selection on purified target. Moka1 blocks Kv1.3 at nanomolar levels that do not inhibit Kv1.1, Kv1.2, or KCa1.1. As a result, moka1 suppresses CD3/28-induced cytokine secretion by T cells without cross-reactive gastrointestinal hyperactivity. The 3D structure of moka1 rationalizes its specificity and validates the engineering approach, revealing a unique interaction surface supported on an ␣-KTx scaffold. This scaffold-based/target-biased strategy overcomes many obstacles to production of selective toxins.mokatoxin ͉ moka1 ͉ phage display ͉ peptide toxin ͉ animal venom
Data curation is one way that libraries are extending traditional services to meet the changing needs of patrons. Requirements from research funders have placed increased pressure on grant recipients to create Data Management Plans and to securely store raw data. Research universities have stepped up to provide comprehensive data support services. Despite discrepancies in funding and staff, smaller institutions can similarly provide robust services by focusing on their strengths, such as interdepartmental collaboration, flexibility, and rapid turnaround time. This article details how librarians at Trinity University adapted the larger practice of curation to meet local data management needs.
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