U.S.-Spain Cooperative Research: Studies of Interface-Folding-Energetics Relationship in Protein Fragment Recognition

这个为期三年的奖项支持美国和西班牙在分子生物学方面的合作研究，获奖者包括纽约市立大学城市学院的玛丽亚·塔萨科和西班牙马德里格拉纳达大学和材料结构中心的何塞·桑切斯·鲁伊斯和洛杉矶·希门尼斯。他们的研究目标是绘制出互补蛋白质片段家族中哪些区域对于它们的重组是必不可少的。具体地说，它们将改变折叠的互补片段之间的界面，同时保持整体结构，以产生与硫氧还蛋白(TRX)模型系统的平坦或交织的界面。他们将阐明界面如何影响从TRX衍生的人工生成的杂二聚体的稳定性和解离/去折叠的速率常数。这位美国研究人员为这一合作带来了设计、工程和产生蛋白质片段以及进行蛋白质片段之间折叠/结合过程的动力学研究方面的专业知识。西班牙研究人员在使用量热法对蛋白质折叠和稳定性进行热力学研究，以及对蛋白质、蛋白质片段及其复合体进行核磁共振研究方面的优势补充了这一点。这项研究将促进我们对发生在生物体内的蛋白质相互作用的理解，并设计出调节蛋白质折叠/结合中亲和力和特异性的方法。

0072029TasaycoThis three-year award, which supports U.S. Spain cooperative research in molecular biology, involves Maria Tasayco of the City University of New York's City College and Jose Sanchez-Ruiz of the University of Granada and Angeles Jimenez of the Center for the Structure of Materials in Madrid, Spain. The objective of their research is to map out which regions from a family of complementary protein fragments are essential for their reassembly. Specifically, they will change the interface surface between folded complementary fragments while maintaining the overall architecture to produce a flat or intertwined interface with the Thioredoxin (Trx) model system. They will clarify how the interface affects the stability and the rate constant of dissociation/unfolding of the artificially generated heterodimers derived from Trx. The U. S. investigator brings to this collaboration expertise in designing, engineering, and generating protein fragments and conducting kinetic studies of folding/binding processes between protein fragments. This is complemented by the Spanish investigators' strengths in thermodynamic studies of protein folding and stability using calorimetry, and in NMR studies of proteins, protein fragments and their complexes. The research will advance our understanding of protein interactions occurring within living organisms and to design ways to modulate the affinity and specificity in protein folding/binding.