A Heterospecific Leucine Zipper Tetramer

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• 作者：Yiqun Deng ; Jie Liu ; Qi Zheng ; Qunnu Li ; Neville R. Kallenbach ; Min Lu
• 刊名：Chemistry & Biology
• 出版年：2008
• 出版时间：22 September 2008
• 年：2008
• 卷：15
• 期：9
• 页码：908-919
• 全文大小：1694 K

文摘

Summary

Protein-protein interactions dictate the assembly of the macromolecular complexes essential for functional networks and cellular behavior. Elucidating principles of molecular recognition governing important interfaces such as coiled coils is a challenging goal for structural and systems biology. We report here that two valine-containing mutants of the GCN4 leucine zipper that fold individually as four-stranded coiled coils associate preferentially in mixtures to form an antiparallel, heterotetrameric structure. X-ray crystallographic analysis reveals that the coinciding hydrophobic interfaces of the hetero- and homotetramers differ in detail, explaining their partnering and structural specificity. Equilibrium disulfide exchange and thermal denaturation experiments show that the 50-fold preference for heterospecificity results from a combination of preferential packing and hydrophobicity. The extent of preference is sensitive to the side chains comprising the interface. Thus, heterotypic versus homotypic interaction specificity in coiled coils reflects a delicate balance in complementarity of shape and chemistry of the participating side chains.