| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
| 권호 | 30권 2호 |
| 발표분야 | 고분자 구조 및 물성 |
| 제목 | The Gating Mechanism in Membrane Protein: an Atomistic Molecular Dynamics Simulation of Cl– Conduction in ClC channel |
| 초록 | ClC channel is a well-known membrane protein that preferentially transports monovalent anions in response to the external stimuli such as membrane voltage, ionic gradient, and pH state. To investigate the mechanism of the anion conduction in molecular level, we perform explicit atomistic molecular dynamics simulation combined with Jarzynski’s theorem1. Especially, we focus on the effect of the protonation state of the glutamate residue in ClC channel on ion conduction. For this purpose, two different initial structures of ClC channel embedded in POPE lipid bilayers are taken from the structure that has been recently revealed by X-ray crystallography with 2.5Å resolution2: One of the structures has the negatively-charged, deprotonated glutamate residue (charged-form), and the other has neutral, protonated glutamate residue (neutral-form). Chlorine ions tied with an imaginary constraint in both forms are pulled with the constant velocity from the extracellular side to the intracellular side. From the simulations, it is found that the glutamate residue acts as a gate that controls opening and closing the pore by which ion conduction is turned on or off. The glutamate residue in the charged form is nearly immobile, strongly interacting with the helix N in which the positive N-terminal facing at the center of the pore. By contrast, the side chain of the glutamate in the neutral form rotates freely, which leads to Cl- conduction across the membrane. The resulting free energy barrier in the charged form is about 23 Kcal/mol which is much higher than that in the neutral forms, as shown in Figure1. These results indicate that ion conduction does not occur when the glutamate residue is negatively-charged in high pH. It is also found that the water molecules only in the extracellular side are in contact with the glutamate residue, which suggests that the pH state in the extracellular side greatly affects the opening probability in ClC channel. In conclusion, the negatively-charged glutamate residue close the ClC channel due to the interaction with the positive N-terminal of helix N, and the glutamate gate opens when the glutamate residue lose its charge in low pH, which results in a pH-responsive ion conduction in ClC channel. Figure 1. the free energy of ion conduction in charged and neutral forms 참고문헌 1. C. Jarzynski, Phys. Rev. Lett., 78, 2690 (1997) 2. R. Dutzler, E. B. Campbell, and R. MacKinnon, Science, 300, 108 (2003) |
| 저자 | 고연조, 허준, 조원호 |
| 소속 | 서울대 |
| 키워드 | protein; biomembrane; molecular dynamics simulation; ClC |
