Metal-binding sites are designed to achieve optimal mechanical and signaling properties.
Many proteins require bound metals to achieve their function. We take advantage of increasing structural data on metal-binding proteins to elucidate three properties: the involvement of metal-binding sites in the global dynamics of the protein, predicted by elastic network models, their exposure/burial to solvent, and their signal-processing properties indicated by Markovian stochastics analysis. Systematic analysis of a data set of 145 structures reveals that the residues that coordinate metal ions enjoy remarkably efficient and precise signal transduction properties. These properties are rationalized in terms of their physical properties: participation in hinge sites that control the softest modes collectively accessible to the protein and occupancy of central positions minimally exposed to solvent. Our observations suggest that metal-binding sites may have been evolutionary selected to achieve optimum allosteric communication. They also provide insights into basic principles for designing metal-binding sites, which are verified to be met by recently designed de novo metal-binding proteins.
Dutta
Anindita
A
Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh, 3064 BST3, 3501 Fifth Avenue, Pittsburgh, PA 15213, USA.
Bahar
Ivet
I
D001665:Binding Sites; D008390:Markov Chains; D008667:Metalloproteins / Q000737:chemistry* / Q000378:metabolism; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D015398:Signal Transduction; D012997:Solvents
D008667:Metalloproteins; D008670:Metals; D012997:Solvents
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