2.A.1.3.22
The Tet38 tetracycline-resistance protein of 450 aas and 14  TMSs of S. aureus (Truong-Bolduc et al., 2005). Tet38 has distinct functions, including drug efflux and host cell attachment and internalization mediated by interaction with host cell CD36. Truong-Bolduc et al. 2021 identified key amino acids involved in different functions. Cysteine substitutions of arginine 106, situated at the junction of TMS 4 and external loop L2, and glycine 151 of motif C on TMS 5, resulted in 8- to 16-fold reductions in Tet38-mediated resistance to tetracycline, with minimal effect on A549 host cell internalization. In contrast, two three-amino-acid deletions, F411P412G413, in external loop L7, situated between TMSs 13 and 14, and D38D39L40, in external loop L1, situated between TMS 1 and 2, led to decreased tetracycline resistance, but only the former affected S. aureus internalization and impaired binding to CD36 (Truong-Bolduc et al. 2021).