Structural and Functional Decomposition of Universal Stress Protein A from M. luteus



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The universal stress protein A (UspA) domain is a protein superfamily of conserved genes found in bacteria, fungi, plants and archaea. Its constitutional responsibility is to initially defend the organism by adjusting gene expression under emerging environmental stresses such as: nutrient starvation, antibiotic and UV radiation. The major purpose of our study was to determine the structure of the UspA 712 molecule from M. luteus, predominantly expressed in the exponential bacterial growth by comparing its structure to other UspA structures, and characterizing their invariant /divergent regions. Principal Component Analysis (PCA) was implemented to examine the relationships between different structures based on their equivalent residues and the axes of maximal variance of the distribution of structures. Ensemble Normal Modes Analysis (eNMA) was applied to examine large-scale motions in the 33 Usp structures to highlight vibrational modes and flexibility in their structures. The structurally invariant core regions in PCA reveal the highly conserved folds in the Usp structures. On the other hand, eNMA displayed the highly flexible looping regions (not located on the invariant Usp scaffold), where potential post-translational modification sites are located. Recent studies present that Usp molecules are not expressed exclusively during stress, but their functions also could be pivotal in different bacterial growth stages. Given that Usp proteins are limited to bacteria, archaea, fungi, and plants (not in humans); regulation in their functions emerge as potential therapeutic targets against bacteria (e.g. dormancy ).