Protein-protein recognition control by modulating electrostatic interactions.
Protein-protein control recognition remains a huge challenge, and its development depends on understanding the chemical and biological mechanisms by which these interactions occur. Here we describe a protein-protein control recognition technique based on the dominant electrostatic interactions occurring between the proteins. We designed a potassium channel inhibitor, BmP05-T, that was 90.32% identical to wild-type BmP05. Negatively charged residues were translocated from the nonbinding interface to the binding interface of BmP05 inhibitor, such that BmP05-T now used BmP05 nonbinding interface as the binding interface. This switch demonstrated that nonbinding interfaces were able to control the orientation of protein binding interfaces in the process of protein-protein recognition. The novel function findings of BmP05-T peptide suggested that the control recognition technique described here had the potential for use in designing and utilizing functional proteins in many biological scenarios.
Han
Song
S
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, P. R. China.
Yin
Shijin
S
Yi
Hong
H
Mouhat
Stéphanie
S
Qiu
Su
S
Cao
Zhijian
Z
Sabatier
Jean-Marc
JM
Wu
Yingliang
Y
Li
Wenxin
W
D000595:Amino Acid Sequence; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D015202:Protein Engineering / Q000379:methods*; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D012604:Scorpion Venoms / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D055672:Static Electricity; D013816:Thermodynamics
C106380:BmP05 toxin; D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms