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 ofSciences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TimTapley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 anacid-activated chaperone allows promiscuous substratebinding
Timothy L. Tapleya,b, Jan L. K?rnera, Madhuri T.Bargea, Julia Hupfelda, Joseph A. Schauertec, Ari Gafnic, UrsulaJakoba and James C. A. Bardwella,b,1
aDepartment of Molecular, Cellular, and DevelopmentalBiology,
cBiophysics Research Division and Department of BiologicalChemistry, and
bHoward Hughes Medical Institute, University of Michigan, AnnArbor, MI 48109
HdeA has been shown to prevent acid-induced aggregation ofproteins. With a mass of only 9.7 kDa, HdeA is one of the smallestchaperones known. Unlike other molecular chaperones, which aretypically complex, multimeric ATP-dependent machines, HdeA is knownto undergo an acid-induced dimer to monomer transition andfunctions at low pH as a disordered monomer without the need forenergy factors. Thus, HdeA must possess features that allow it tobind substrates and regulate substrate affinity in a small andenergy-independent package. To understand better how HdeAaccomplishes this, we studied the conformational changes thataccompany a shift to low pH and substrate binding. We find that theacid-induced partial unfolding and monomerization that lead to HdeAactivation occur very rapidly (k >3.5 s?1). Activation exposesthe hydrophobic dimer interface, which we found to be critical forsubstrate binding. We show by intramolecular FRET that thepartially unfolded character of active HdeA allows the chaperone toadopt different conformations as required for the recognition andhigh-affinity binding of different substrate proteins. Theseefficient adaptations help to explain how a very small protein israpidly activated and can bind a broad range of substrate proteinsin a purely pH-regulated manner.
抗金属蛋白酶和其它蛋白酶抗体（Invitek）