Lundbaek J A, Andersen O S
Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021 USA.
Biophys J. 1999 Feb;76(2):889-95. doi: 10.1016/S0006-3495(99)77252-8.
Hydrophobic interactions between a bilayer and its embedded membrane proteins couple protein conformational changes to changes in the packing of the surrounding lipids. The energetic cost of a protein conformational change therefore includes a contribution from the associated bilayer deformation energy (DeltaGdef0), which provides a mechanism for how membrane protein function depends on the bilayer material properties. Theoretical studies based on an elastic liquid-crystal model of the bilayer deformation show that DeltaGdef0 should be quantifiable by a phenomenological linear spring model, in which the bilayer mechanical characteristics are lumped into a single spring constant. The spring constant scales with the protein radius, meaning that one can use suitable reporter proteins for in situ measurements of the spring constant and thereby evaluate quantitatively the DeltaGdef0 associated with protein conformational changes. Gramicidin channels can be used as such reporter proteins because the channels form by the transmembrane assembly of two nonconducting monomers. The monomerleft arrow over right arrow dimer reaction thus constitutes a well characterized conformational transition, and it should be possible to determine the phenomenological spring constant describing the channel-induced bilayer deformation by examining how DeltaGdef0 varies as a function of a mismatch between the hydrophobic channel length and the unperturbed bilayer thickness. We show this is possible by analyzing experimental studies on the relation between bilayer thickness and gramicidin channel duration. The spring constant in nominally hydrocarbon-free bilayers agrees well with estimates based on a continuum analysis of inclusion-induced bilayer deformations using independently measured material constants.
双层膜与其嵌入的膜蛋白之间的疏水相互作用将蛋白质构象变化与周围脂质堆积的变化联系起来。因此,蛋白质构象变化的能量成本包括相关双层膜变形能(ΔGdef0)的贡献,这为膜蛋白功能如何依赖于双层膜材料特性提供了一种机制。基于双层膜变形的弹性液晶模型的理论研究表明,ΔGdef0应该可以通过一个唯象线性弹簧模型来量化,在该模型中,双层膜的力学特性被集中到一个单一的弹簧常数中。弹簧常数与蛋白质半径成比例,这意味着可以使用合适的报告蛋白来原位测量弹簧常数,从而定量评估与蛋白质构象变化相关的ΔGdef0。短杆菌肽通道可以用作这样的报告蛋白,因为通道由两个非导电单体的跨膜组装形成。单体⇄二聚体反应因此构成了一个特征明确的构象转变,并且应该可以通过研究ΔGdef0如何随疏水通道长度与未受扰动的双层膜厚度之间的不匹配而变化来确定描述通道诱导的双层膜变形的唯象弹簧常数。我们通过分析关于双层膜厚度与短杆菌肽通道持续时间之间关系的实验研究表明这是可能的。名义上无烃双层膜中的弹簧常数与基于使用独立测量的材料常数对包含物诱导的双层膜变形进行连续分析的估计值非常吻合。