Abstract：
Complex V or FoF1-ATPase is a multimeric protein found in bioenergetic membranes of cells and organelles like mitochondria/chloroplasts. The popular perception on Complex V deems it as a reversible molecular motor, working bi-directionally (breaking or making ATP) via a conformation-change based chemiosmotic rotary ATP synthesis (CRAS) mechanism, driven by proton-gradients or trans-membrane potential (TMP). In continuance of our pursuits against the CRAS model of cellular bioenergetics, herein we demonstrate the validity of the murburn model based in diffusible reactive (oxygen) species (DRS/DROS). Supported by new in silico derived data (that there are ∼12 adenosine nucleotide binding sites on the F1 bulb and not merely 3 sites, as perceived earlier), available structural information, known experimental observations, and thermodynamic/kinetic considerations (that de-solvation of protons from hydronium ions is facile), we deduce that Complex V serves as a physiological chemostat and a murzyme (enzyme working via murburn scheme, employing DRS). That is- Complex V uses ATP (via consumption at ε or proteins of F1 module) as a Michaelis-Menten substrate to serve as a pH-stat by inletting protons via the c-ring of Fo module. Physiologically, Complex V also functions as a murzyme by presenting ADP/Pi (or their reaction intermediates) on the αβ bulb, thereby enabling greater opportunities for DRS/proton-assisted ATP formation. Thus, the murburn paradigm succeeds the CRAS hypothesis for explaining the role of oxygen in mitochondrial physiologies of oxidative phosphorylation, thermogenesis, TMP and homeostasis.Communicated by Ramaswamy H. Sarma.
摘要：
复合物V或FoF1-ATP酶是在细胞和细胞器如线粒体/叶绿体的生物能量膜中发现的多聚体蛋白。关于复杂V的普遍看法认为它是可逆的分子马达，通过基于构象变化的化学渗透旋转ATP合成（CRAS）机制双向工作（破坏或制造ATP），由质子梯度或跨膜电位（TMP）驱动。为了继续我们对细胞生物能学的CRAS模型的追求，在本文中，我们证明了基于可扩散反应（氧）物质（DRS/DROS）的murburn模型的有效性。由新的计算机衍生数据支持（F1灯泡上有~12个腺苷核苷酸结合位点，而不仅仅是3个位点，如前所述)，可用的结构信息，已知的实验观察，和热力学/动力学考虑（质子从水合氢离子去溶剂化是容易的），我们推导出复合物V作为生理恒化器和一个murzyme(酶通过murburn方案工作，采用DRS)。即-复合物V使用ATP（通过消耗ε或F1模块的蛋白质）作为Michaelis-Menten底物，通过经由Fo模块的c环输入质子来充当pHstat。生理学上,复合物V还通过将ADP/Pi（或其反应中间体）呈递在αβ球上而起到杀菌酶的作用，从而为DRS/质子辅助ATP形成提供更大的机会。因此，murburn范式成功的CRAS假说，用于解释氧在线粒体氧化磷酸化生理中的作用，产热,TMP和体内平衡。由RamaswamyH.Sarma沟通。
