Picornaviral IRES elements are essential for initiating the cap-independent viral translation. However, three-dimensional structures of these elements remain elusive. Here, we report a 2.84-Å resolution crystal structure of hepatitis A virus IRES domain V (dV) in complex with a synthetic antibody fragment—a crystallization chaperone. The RNA adopts a three-way junction structure, topologically organized by an adenine-rich stem-loop motif. Despite no obvious sequence homology, the dV architecture shows a striking similarity to a circularly permuted form of encephalomyocarditis virus J-K domain, suggesting a conserved strategy for organizing the domain architecture. Recurrence of the motif led us to use homology modeling tools to compute a 3-dimensional structure of the corresponding domain of foot-and-mouth disease virus, revealing an analogous domain organizing motif. The topological conservation observed among these IRESs and other viral domains implicates a structured three-way junction as an architectural scaffold to pre-organize helical domains for recruiting the translation initiation machinery.
Our group is broadly interested in the chemistry and biochemistry of nucleic acids with particular emphasis on RNA and RNA catalysis. The laboratory integrates areas of organic chemistry, physical chemistry, enzymology and molecular biology to gain a fundamental understanding of nucleic acid structure and mechanisms of RNA catalysis. Using the principles and techniques of organic chemistry and molecular biology, we manipulate the structure of RNA molecules at precise locations in ways that are designed to answer very specific questions about biological function. With a team consisting of people trained in EPR, Optical Tweezers, Fluorescence spectroscopy, MRI and X-Ray Crystallography, protein engineering and Nucleic acid synthetic chemistry, we are equipped to take on varied challenges in RNA chemistry and biology.
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