Structural basis for the autoprocessing of zinc metalloproteases in the thermolysin family英文文献.pdfVIP

Structural basis for the autoprocessing of zinc metalloproteases in the thermolysin family a,b b c a a a a c b Xiang Gao , Jue Wang , Da-Qi Yu , Fei Bian , Bin-Bin Xie , Xiu-Lan Chen , Bai-Cheng Zhou , Lu-Hua Lai , Zhi-Xin Wang , Jia-Wei Wub,1, and Yu-Zhong Zhanga,1 aState Key Laboratory of Microbial Technology, Marine Biotechnology Research Center, Shandong University, Jinan 250100, China; bThe Ministry of Education Key Laboratory of Bioinformatics, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China; and cCenter for Theoretical Biology, Peking University, Beijing 100871, China Edited by Brian W. Matthews, University of Oregon, Eugene, OR, and approved August 18, 2010 (received for review April 27, 2010) Thermolysin-like proteases (TLPs), a large group of zinc metallopro- is still unknown. Biochemical studies have revealed that the teases, are synthesized as inactive precursors. TLPs with a long maturation of TLPs occurs through autoprocessing and that this propeptide (∼200 residues) undergo maturation following autop- autoprocessing pathway is mediated by the propeptide (14, 15). rocessing through an elusive molecular mechanism. We report The propeptide in TLPs and in some serine proteases is also the first two crystal structures for the autoprocessed complexes referred to as an intramolecular chaperone (IMC), as it is essen- of a typical TLP, MCP-02. In the autoprocessed complex, Ala205 tial for the folding of the catalytic domain but is not required shifts upward by 33 Å from the previously covalently linked resi- for its function (16). In some serine proteases, such as subtilisin, due, His204, indica