GerAB

<i>Bacillus</i> <i>subtilis</i> forms dormant spores upon nutrient depletion. Germinant receptors (GRs) in spore’s inner membrane respond to ligands such as L-alanine, and trigger spore germination. In <i>B. subtilis</i> spores, GerA is the major GR, and has three subunits, GerAA, GerAB, and GerAC. L-Alanine activation of GerA requires all three subunits, but which binds L-alanine is unknown. To date, how GRs trigger germination is unknown, in particular due to lack of detailed structural information about B subunits. Using homology modelling with molecular dynamics (MD) simulations, we present structural predictions for the integral membrane protein GerAB. These predictions indicate that GerAB is an alpha-helical transmembrane protein containing a water channel. The MD simulations with free L-alanine show that alanine binds transiently to specific sites on GerAB. These results provide a starting point for unraveling the mechanism of L-alanine mediated signaling by GerAB, which may facilitate early events in spore germination.

枯草芽孢杆菌（Bacillus subtilis）在营养匮乏条件下会形成休眠孢子。孢子内膜中的萌发受体（Germinant Receptors, GRs）可识别L-丙氨酸（L-alanine）等配体，并触发孢子萌发。在枯草芽孢杆菌的孢子中，GerA为主要的萌发受体，其包含GerAA、GerAB与GerAC三个亚基。L-丙氨酸激活GerA需要这三个亚基共同参与，但目前尚不明确哪一个亚基能够结合L-丙氨酸。迄今为止，学界尚未明确GRs触发孢子萌发的具体机制，究其原因，主要是缺乏B亚基的详细结构信息。本研究通过同源建模（homology modelling）结合分子动力学（Molecular Dynamics, MD）模拟，对整合膜蛋白GerAB开展了结构预测。预测结果显示，GerAB为一类包含水通道的α螺旋（alpha-helical）跨膜蛋白。针对游离L-丙氨酸的MD模拟结果表明，丙氨酸会短暂结合于GerAB的特定位点。本研究结果为阐明GerAB介导的L-丙氨酸信号转导机制提供了基础，或可推动孢子萌发早期事件的相关研究。