生命科學與醫學獎
2012

蛋白質分子參與組織和催化大部份細胞的代謝和生長活動。蛋白質由長線型氨基酸鏈組成，其化學性質和相互作用決定了最後的折疊形狀及所有生物細胞內酶的功能特性和結構。一些蛋白質可自發地在試管中折疊，但有些則需要蛋白質「分子伴侶」引導其在細胞內或試管中進行折疊。自1989年始，弗朗茲—烏爾里奇・哈特爾 (Franz-Ulrich Hartl) 和亞瑟・霍里奇 (Arthur L Horwich) 首先一起工作，進而在各自的實驗室，確定分子伴侶在細胞電廠(線粒體)和細胞液(細胞質)內介入蛋白質折疊。

哈特爾和霍里奇在研究的初期，探討由於酵母突變導致線粒體內的單一蛋白質折疊及多亞基蛋白質折疊的缺損。他們在試管中證實了一種被稱為GroE的分子伴侶的活動，而後通過詳細研究，利用高清晰度的結構分析，顯現出其折疊腔的精確原子構造。霍里奇亦獨自與耶魯大學卓越的結構生物學家保羅・西格勒 (Paul Sigler) 合作，解決了折疊機制的原子結構。另外，哈特爾和霍里奇分別顯示了GroE在封閉腔內捕捉了一個未折疊的多肽，在ATP能量的作用下，能在不同階段改變其形狀，直到最後釋放出完整折疊的蛋白質產物。

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.