TY  - JOUR
AU  - Alfonso-Prieto, Mercedes
AU  - Giorgetti, Alejandro
AU  - Carloni, Paolo
TI  - Multiscale simulations on human Frizzled and Taste2 GPCRs
JO  - Current opinion in structural biology
VL  - 55
SN  - 0959-440X
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - FZJ-2019-02680
SP  - 8-16
PY  - 2019
AB  - Recently, molecular dynamics simulations, from all atom and coarse grained to hybrid methods bridging the two scales, have provided exciting functional insights into class F (Frizzled and Taste2) GPCRs (about 40 members in humans). Findings include: (i) The activation of one member of the Frizzled receptors (FZD4) involves a bending of transmembrane helix TM7 far larger than that in class A GPCRs. (ii) The affinity of an anticancer drug targeting another member (Smoothened receptor) decreases in a specific drug-resistant variant, because the mutation ultimately disrupts the binding cavity and affects TM6. (iii) A novel two-state recognition mechanism explains the very large agonist diversity for at least one member of the Taste2 GPCRs, hTAS2R46.
LB  - PUB:(DE-HGF)16
C6  - pmid:30933747
UR  - <Go to ISI:>//WOS:000482514400004
DO  - DOI:10.1016/j.sbi.2019.02.009
UR  - https://juser.fz-juelich.de/record/862342
ER  -