Structural basis for recognition of the tumor suppressor protein PTPN14 by the oncoprotein E7 of human papillomavirus
Fig 2
Crystal structure of the PTPN14–HPV18 E7 complex.
(A) Crystal structure of the complex. PTPN14 (violet) and HPV E7 (green) are presented as ribbon drawings with the secondary structure labels according to the order of their appearance in the primary sequence. The catalytic cysteine residue of PTPN14 (Cys1121) and zinc ion (present as a red sphere)–coordinating four cysteine residues of HPV18 E7 (Cys65, Cys68, Cys98, and Cys101) are shown in sticks and labeled. (B) Intermolecular interaction is shown in two views. PTPN14 and HPV18 E7 residues critically involved in the complex formation are shown in sticks and labeled. Residues that are selected to be mutated in c are marked with underlines. Dotted lines represent electrostatic interaction between Glu1095 of PTPN14 and Arg84 of HPV18 E7. (C) ITC measurements. The KD values between wild-type or mutant proteins were calculated as was in Fig 1B. Introduction of R84A and L91A mutations into HPV18 E7 or F1044S, G1055Q, and E1095A mutations into PTPN14 abrogated the binding interaction between the two proteins. HPV, human papillomavirus; ITC, isothermal titration calorimetry; MBP, maltose binding protein; PTPN14, nonreceptor-type protein tyrosine phosphatase 14.