Abstract
Drosha and Dicer are RNase III family members of classes II and III, respectively, which play a major role in the maturation of micro-RNAs. The two proteins share similar domain arrangement and overall fold despite no apparent sequence homology. The overall structural and catalytic reaction similarity of both proteins, on the one hand, and differences in the substrate and its binding mechanisms, on the other, suggest that both proteins also share dynamic similarities and dissimilarities. Since dynamics is essential for protein function, a comparison at their dynamics level is fundamental for a complete understanding of the overall relations between these proteins. In this study, we present a dynamical comparison between human Drosha and Giardia Dicer. Gaussian Network Model and Anisotropic Network Model modes of motion of the proteins are calculated. Dynamical comparison is performed using global and local dynamic programming algorithms for aligning modes of motion. These algorithms were recently developed based on the commonly used Needleman-Wunsch and Smith-Waterman algorithms for global and local sequence alignment. The slowest mode of Drosha is different from that of Dicer due to its more bended posture and allow the motion of the double-stranded RNA-binding domain toward and away from its substrate. Among the five slowest modes dynamics similarity exists only for the second slow mode of motion of Drosha and Dicer. In addition, high local dynamics similarity is observed at the catalytic domains, in the vicinity of the catalytic residues. The results suggest that the proteins exert a similar catalytic mechanism using similar motions, especially at the catalytic sites.
Highlights
Sequence and structure alignment algorithms are long standing techniques to study proteins
Sequence alignment algorithms [1,2,3] identify residue conservation, while structure-based classification algorithms like CATH [4], SCOP [5], and DALI [6] provide a good overview of the entire protein structure universe
We examine the dynamics similarity and dissimilarities of human Drosha and Giardia Dicer by comparing their Gaussian Network Model (GNM) and Anisotropic Network Model (ANM) modes of motions, using recently developed global [13] and local [46] mode alignment algorithms
Summary
Sequence and structure alignment algorithms are long standing techniques to study proteins. Dynamical comparison between Drosha and Dicer for comprehending the protein structure–dynamics–function relationship. Such an understanding can stem from a comparison of the dynamics of related proteins or the same protein in different states. Dynamical comparison of proteins was limited to conserved residues between related proteins [7,8,9]. We [10,11,12,13] and others [14,15,16,17] have developed several tools and techniques for comparison of protein dynamics that are sequence and structure independent, contributing to the development of the field of comparative dynamics. The dynamical similarity between human Drosha and Giardia Dicer is presented in this study
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