生命科学与医学奖
2012

蛋白质分子参与组织和催化大部份细胞的代谢和生长活动。蛋白质由长线型氨基酸链组成，其化学性质和相互作用决定了最后的折叠形状及所有生物细胞内酶的功能特性和结构。一些蛋白质可自发地在试管中折叠，但有些则需要蛋白质「分子伴侣」引导其在细胞内或试管中进行折叠。自1989年始，弗朗兹—乌尔里奇・哈特尔 (Franz-Ulrich Hartl) 和亚瑟・霍里奇 (Arthur L Horwich) 首先一起工作，进而在各自的实验室，确定分子伴侣在细胞电厂(线粒体)和细胞液(细胞质)内介入蛋白质折叠。

哈特尔和霍里奇在研究的初期，探讨由於酵母突变导致线粒体内的单一蛋白质折叠及多亚基蛋白质折叠的缺损。他们在试管中证实了一种被称为GroE的分子伴侣的活动，而后通过详细研究，利用高清晰度的结构分析，显现出其折叠腔的精确原子构造。霍里奇亦独自与耶鲁大学卓越的结构生物学家保罗・西格勒 (Paul Sigler) 合作，解决了折叠机制的原子结构。另外，哈特尔和霍里奇分别显示了GroE在封闭腔内捕捉了一个未折叠的多肽，在ATP能量的作用下，能在不同阶段改变其形状，直到最后释放出完整折叠的蛋白质产物。

Protein molecules are long, complex strings of amino acids that have many possible ways of folding into a compact shape, yet they somehow fold beautifully in the crowded interior environment of a cell.  Folding is guided by the sequence of amino acids in a protein but sometimes this process goes bad when proteins are changed because of mutation or when surfaces that are incompatible with the water environment of the cell cytoplasm become exposed during the folding process. Cells have evolved molecular chaperones, such as GroEL, to help shield such surfaces and to provide a protected environment in which to complete the folding process. The surfaces of this remarkable machinery are very forgiving. They actually utilize metabolic energy (i.e., ATP hydrolysis) to alternate their physical chemistry between hydrophobic states and hydrophilic states, which restarts the folding when it stalls and expels the protein when folding is completed. In the case of GroEL, a molecular chaperone shaped like a test tube, access to the cavity is highly selective and limited to only newly-made proteins or those purposely unfolded to repair damage or mistakes.

The 2012 Shaw Prize in Life Science and Medicine is awarded to Ulrich Hartl, Director, Max Planck Institute of Biochemistry in Martisried, Germany and Arthur Horwich, Professor of Genetics and Investigator of the Howard Hughes Medical Institute, Yale University School of Medicine.  Together, these two investigators identified the chaperones and their mechanism of action in the cell powerhouse, the mitochondrion, and in the cell sap, the cytoplasm.