POSTECH 생명과학과
Seminar
Seminar

Cryo-EM structure of human P-glycoprotein in the outward-facing confor…

  • Hit 126
  • Writer 최고관리자
  • 2018-09-19

본문

▶Subject: Cryo-EM structure of human P-glycoprotein in the outward-facing conformation

 ▶Speaker: Youngjin Kim, Ph.D (Department of Chemistry, KAIST)

 ▶Date: 4:00PM/Sept. 20(Thur.)/ 2018

▶Place: Auditorium(1F), Postech Biotech Center

▶Abctract
The  Multidrug  resistance  to  chemotherapeutics  is  a  major  obstacle  to  successful cancer  treatment.  ATP-binding  cassette  (ABC)  transporter  are  often  the  culprits. These  membrane  bound  transporter  utilize  the  energy  of  ATP  binding  and hydrolysis to activity pump chemotherapy drugs from cells before they can reach their intracellular target, thus shielding the cells from the drug’s cytotoxic effects. Several  different  ABC  transporters  have  been  implicated  in  the  phenomenon including P-glycoprotein (P-gp), the breast cancer resistance protein (ABCG2), and the  multidrug  resistance  protein  (MRP1).  P-glycoprotein  extrudes  toxic  molecules and  drugs  from  cells  through  ATP-powered  conformational  changes.  Despite decades  of  effort,  only  the  structures  of  the  inward-facing  conformation  of  P- glycoprotein are available.
To better understand the physiological roles of P-glycoprotein, we have solve high- resolution electron cryo-microscopy (cryo-EM) structure of human P-glycoprotein in the  outward-facing  conformation.  The  two  nucleotide-binding  domains  form  a closed dimer occluding two ATP molecules. The drug-binding cavity observed in the inward-facing  structures  is  re-orientated  toward  the  extracellular  space  and compressed to preclude substrate binding. Those features of structure elucidate the role of ATP in substrate release from the transporter. The structure evokes a model in  which  the  dynamic  nature  of  P-glycoprotein  enables  translocation  of  a  large variety of substrates.

▶Contact: Department of Life Sciences (Tel. 279-2721)

* This seminar will be given in English.
please refrain from taking photos during seminars. *

Top