Apostolovic Bojana, Klok Harm-Anton
E cole Polytechnique Fédé rale de Lausanne, Institut des Matériaux, Laboratoire des Polymères Bâtiment MXD, Station 12, 1015 Lausanne, Switzerland.
Biomacromolecules. 2008 Nov;9(11):3173-80. doi: 10.1021/bm800746e. Epub 2008 Oct 21.
This manuscript reports on the self-assembly properties of two complementary peptide sequences, E3 and K3, which are derived from the known IAAL E3/K3 heterodimeric coiled coil motif. Circular dichroism spectroscopy, analytical ultracentrifugation, and fluorescence resonance energy transfer experiments indicated that a stoichiometric mixture of these two peptides forms a stable heterodimeric coiled coil at pH 7. At pH 5, in contrast, the E3/K3 heterodimeric coiled coil is unstable and unfolds to generate E3 homotrimers that coexist with K3 unimers and a small fraction of K3 homodimers. This pH-induced unfolding transition was unprecedented for this coiled coil motif but is of interest as it occurs within a physiologically relevant pH range, as it is encountered, for example, during cellular uptake via the endosomal pathway. This feature, in combination with the relatively short length of the E3 and K3 peptides and the high stability of the E3/K3 coiled coil at pH 7 makes this folding motif very attractive for the development of noncovalent polymer therapeutics and self-assembled biohybrid hydrogels.
本手稿报道了两个互补肽序列E3和K3的自组装特性，它们源自已知的IAAL E3/K3异源二聚体卷曲螺旋基序。圆二色光谱、分析超速离心和荧光共振能量转移实验表明，这两种肽的化学计量混合物在pH 7时形成稳定的异源二聚体卷曲螺旋。相比之下，在pH 5时，E3/K3异源二聚体卷曲螺旋不稳定并展开，生成与K3单体和一小部分K3同源二聚体共存的E3同源三聚体。这种pH诱导的展开转变对于这种卷曲螺旋基序来说是前所未有的，但因其发生在生理相关的pH范围内而备受关注，例如在通过内体途径进行细胞摄取过程中就会遇到这种情况。这一特性，再加上E3和K3肽相对较短的长度以及E3/K3卷曲螺旋在pH 7时的高稳定性，使得这种折叠基序对于非共价聚合物疗法和自组装生物杂交水凝胶的开发非常有吸引力。
