密歇根大学和霍华德休斯医学研究所的科学家发现了一种命名为HdeA的蛋白质分子伴侣，这种蛋白质分子伴侣能够阻止大肠杆菌免受胃酸的干扰，并能防止蛋白质形成破坏性的团块。这篇研究报告发表在近期的Proceedings of the National Academy of Sciences杂志网络版上。
像大肠杆菌之类的致病菌，一旦被摄入到人体或动物体内并接触到胃酸，将导致致病菌自身的蛋白质处于非折叠状态，这种非折叠状态干扰蛋白质正常功能，如果此时蛋白质伴侣HdeA没有介入，将很快引起细菌死亡。当病原菌进入胃中，HdeA能够与非折叠的蛋白质紧密结合，通过结合到细菌的蛋白质上，伴侣分子能够保护细菌免于死亡。
该课题组发现，当细菌进入到小肠的碱性环境中，HdeA释放非折叠蛋白并使蛋白质重新折叠成正确的构象，而不是聚集成团。据主要研究人员Tim Tapley介绍，因为一旦非折叠蛋白被HdeA同时释放，则很容易聚集起来，导致细菌死亡，HdeA蛋白采用了一种独特的“定时释放”机制。在该研究中，研究人员观察到，蛋白质伴侣HdeA逐渐释放非折叠蛋白，这使其更倾向于重新折叠成正确构象。
大多数分子伴侣在发挥功能时需要大量的细胞能量，但HdeA能够利用周围环境中pH改变产生的能量，如细菌胃中的酸性环境转移到微碱性的小肠环境中。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS March 24, 2009, doi: 10.1073/pnas.0811811106
Structural plasticity of an acid-activated chaperone allows promiscuous substrate binding
Timothy L. Tapleya,b, Jan L. K?rnera, Madhuri T. Bargea, Julia Hupfelda, Joseph A. Schauertec, Ari Gafnic, Ursula Jakoba and James C. A. Bardwella,b,1
aDepartment of Molecular, Cellular, and Developmental Biology,
cBiophysics Research Division and Department of Biological Chemistry, and
bHoward Hughes Medical Institute, University of Michigan, Ann Arbor, MI 48109
HdeA has been shown to prevent acid-induced aggregation of proteins. With a mass of only 9.7 kDa, HdeA is one of the smallest chaperones known. Unlike other molecular chaperones, which are typically complex, multimeric ATP-dependent machines, HdeA is known to undergo an acid-induced dimer to monomer transition and functions at low pH as a disordered monomer without the need for energy factors. Thus, HdeA must possess features that allow it to bind substrates and regulate substrate affinity in a small and energy-independent package. To understand better how HdeA accomplishes this, we studied the conformational changes that accompany a shift to low pH and substrate binding. We find that the acid-induced partial unfolding and monomerization that lead to HdeA activation occur very rapidly (k <3.5 s?1). Activation exposes the hydrophobic dimer interface, which we found to be critical for substrate binding. We show by intramolecular FRET that the partially unfolded character of active HdeA allows the chaperone to adopt different conformations as required for the recognition and high-affinity binding of different substrate proteins. These efficient adaptations help to explain how a very small protein is rapidly activated and can bind a broad range of substrate proteins in a purely pH-regulated manner.
