Molecular Dynamics Simulations of the TrkH Membrane Protein

被引:22
作者
Domene, Carmen [1 ]
Furini, Simone [1 ,2 ]
机构
[1] Univ Oxford, Phys & Theoret Chem Lab, Dept Chem, Oxford OX1 3QZ, England
[2] Univ Siena, Dept Med Surg & Bioengn, I-53100 Siena, Italy
基金
英国工程与自然科学研究理事会;
关键词
POTASSIUM CHANNELS; SELECTIVITY FILTER; FREE-ENERGY; ION CONDUCTION; K+-CHANNELS; PERMEATION; WATER; ENERGETICS; MECHANISM; MODELS;
D O I
10.1021/bi201586n
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
TrkH is a transmembrane protein that mediates uptake of K+ through the cell membrane. Despite the recent determination of its crystallographic structure, the nature of the permeation mechanism is still unknown, that is, whether K+ ions move across TrkH by active transport or passive diffusion. Here, molecular dynamics simulations and the umbrella sampling technique have been employed to shed light on this question. The existence of binding site S3 and two alternative binding sites have been characterized. Analysis of the coordination number renders values that are almost constant, with a full contribution from the carbonyls of the protein only at S3. This observation contrasts with observations of K+ channels, where the contribution of the protein to the coordination number is roughly constant in all four binding sites. An intramembrane loop is found immediately after the selectivity filter at the intracellular side of the protein, which obstructs the permeation pathway, and this is reflected in the magnitude of the energy barriers.
引用
收藏
页码:1559 / 1565
页数:7
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