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This paper describes our analysis of the complex head‐neck system using a combination of experimental and modeling approaches. Dynamical analysis of head movements and EMG activation elicited by perturbation of trunk position has examined functional contributions of biomechanically and neurally generated forces in lumped systems with greatly simplified kinematics. This has revealed that visual and voluntary control of neck muscles and the dynamic and static vestibulocollic and cervicocollic reflexes preferentially govern head‐neck system state in different frequency domains. It also documents redundant control, which allows the system to compensate for lesions and creates a potential for substantial variability within and between subjects. Kinematic studies have indicated the existence of reciprocal and co‐contraction strategies for voluntary force generation, of a vestibulocollic strategy for stabilizing the head during body perturbations and of at least two strategies for voluntary head tracking. Each strategy appears to be executed by a specific muscle synergy that is presumably optimized to efficiently meet the demands of the task.

The fidelity of protein synthesis depends on specific tRNA aminoacylation by aminoacyl-tRNA synthetase enzymes, which in turn depends on the recognition of the identity of particular nucleotides and structural features in the substrate tRNA. These features generally reside within the acceptor helix, the anticodon stemloop, and in some systems the variable pocket of the tRNA. In the alanine system, fidelity is ensured by a G⅐U wobble base pair located at the third position within the acceptor helix of alanine tRNA. We have investigated the activity of mutant alanine tRNAs to explore the mechanism of enzyme recognition. Here we show that the mismatched pair C-C is an excellent substitute for G⅐U in alanine-tRNA-knockout cells. A structural investigation by NMR spectroscopy of the C-C RNA acceptor end reveals that the two cytosines are intercalated into the helix, and that C-C exists in multiple conformations. Structural heterogeneity also is present in the wild-type G⅐U RNA, whereas inactive Watson-Crick helices are structurally rigid. The correlation between functional and structural data suggests that the G⅐U pair provides a distinctive structure and a point of deformability that allow the tRNA acceptor end to fit into the active site of the alanyl-tRNA synthetase. Fidelity is ensured because noncognate and inactive mutant tRNAs are bound in the active site in an incorrect conformation that reduces enzymatic activity.A minoacylation of Escherichia coli tRNA Ala by its cognate alanyl-tRNA synthetase (AlaRS) enzyme depends on a G⅐U wobble base pair § in the acceptor helix (Fig. 1); this feature is critical for aminoacylation and can confer partial alanine acceptance on other noncognate tRNAs (1, 2). The features that allow its recognition are likely to include direct interactions with distinctive atomic groups and indirect recognition of the structural and dynamic information encoded in the sequence of the G⅐U pair and its immediate context. The G⅐U wobble base pair provides specific recognition signals in numerous RNAs, ranging from ribosomal RNA and splicing regulatory signals (3) to RNA enzymes (4). A detailed understanding of recognition mechanisms of the G⅐U pair is still lacking. Therefore, tRNA Ala provides not only an important system to understand how fidelity in protein synthesis is ensured, but also a paradigm to dissect the features that allow such a widespread role for the G⅐U pair as a distinctive recognition tag.Here we report the remarkable observation that replacing the G⅐U wobble pair with a C-C mispair preserves tRNA Ala aminoacylation in vivo. An acceptor minihelix RNA containing the C-C substitution has been analyzed by high-resolution NMR spectroscopy and compared with wild-type G⅐U RNA and inactive G⅐C and A⅐U mutant RNAs. The data demonstrate that the two cytosines are intercalated within the acceptor helix, and that C-C exists in multiple conformations in equilibrium on the s-ms time scale. The structure at and around G⅐U and C-C is significantly more mobile than that of Watson-Crick base ...