Structure and Function of the Virulence-Associated High-Temperature Requirement A of Mycobacterium tuberculosis
详细信息 查看全文
- 作者：Nilofar N. MohamedMohaideen ; Satheesh K. Palaninathan ; Paul M. Morin ; Brad J. Williams ; Miriam Braunstein ; Shane E. Tichy ; Joseph Locker ; David H. Russell ; William R. Jacobs Jr. ; James C. Sacchettini
- 刊名：Biochemistry
- 出版年：2008
- 出版时间：June 10, 2008
- 年：2008
- 卷：47
- 期：23
- 页码：6092 - 6102
- 全文大小：8277K
- 年卷期：v.47,no.23(June 10, 2008)
- ISSN：1520-4995
文摘
The high-temperature requirement A (HtrA) family of serine proteases has been shown to play an important role in the environmental and cellular stress damage control system in Escherichia coli. Mycobacterium tuberculosis (Mtb) has three putative HtrA-like proteases, HtrA1, HtrA2, and HtrA3. The deletion of htrA2 gives attenuated virulence in a mouse model of TB. Biochemical analysis reveals that HtrA2 can function both as a protease and as a chaperone. The three-dimensional structure of HtrA2 determined at 2.0 Å resolution shows that the protease domains form the central core of the trimer and the PDZ domains extend to the periphery. Unlike E. coli DegS and DegP, the protease is naturally active due to the formation of the serine protease-like catalytic triad and its uniquely designed oxyanion hole. Both protease and PDZ binding pockets of each HtrA2 molecule are occupied by autoproteolytic peptide products and reveal clues for a novel autoregulatory mechanism that might have significant importance in HtrA-associated virulence of Mtb.