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Protein thermal denaturation is modulated by central residues in the protein structure network
Author(s) -
Souza Valquiria P.,
Ikegami Cecília M.,
Arantes Guilherme M.,
Marana Sandro R.
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13659
Subject(s) - chemistry , protein folding , residue (chemistry) , protein tertiary structure , denaturation (fissile materials) , protein structure , thermal stability , biophysics , crystallography , biochemistry , biology , nuclear chemistry , organic chemistry
Network structural analysis, known as residue interaction networks or graphs ( RIN or RIG , respectively) or protein structural networks or graphs ( PSN or PSG , respectively), comprises a useful tool for detecting important residues for protein function, stability, folding and allostery. In RIN , the tertiary structure is represented by a network in which residues (nodes) are connected by interactions (edges). Such structural networks have consistently presented a few central residues that are important for shortening the pathways linking any two residues in a protein structure. To experimentally demonstrate that central residues effectively participate in protein properties, mutations were directed to seven central residues of the β‐glucosidase Sfβgly (β‐ d ‐glucoside glucohydrolase; EC 3.2.1.21 ). These mutations reduced the thermal stability of the enzyme, as evaluated by changes in transition temperature ( T m ) and the denaturation rate at 45 °C. Moreover, mutations directed to the vicinity of a central residue also caused significant decreases in the T m of Sfβgly and clearly increased the unfolding rate constant at 45 °C. However, mutations at noncentral residues or at surrounding residues did not affect the thermal stability of Sfβgly. Therefore, the data reported in the present study suggest that the perturbation of the central residues reduced the stability of the native structure of Sfβgly. These results are in agreement with previous findings showing that networks are robust, whereas attacks on central nodes cause network failure. Finally, the present study demonstrates that central residues underlie the functional properties of proteins.