Progress on the Anthrax Toxin and Its Receptor

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1 ISSN CN ΠQ Chinese Journal of Biochemistry and Molecular Biology 18 (6) : , 3 (, ) 3 : (protective antigen, PA) (lethal factor, LF) (edema factor, EF) LF PA (anthrax toxin receptor, ATR) cdna,, Q71,Q785 Progress on the Anthrax Toxin and Its Receptor LI Yan2ling,LIU Cheng2yi 3 ( The Information Biology Group of Laboratory of Light Transmission Optics, South China Normal University, Guangzhou , China) Abstract The recent progress of the study on the anthrax toxin have been reviewed The anthrax toxin con2 sists of three proteins : protective antigen (PA), lethal factor (LF) and edema factor ( EF) PA binds to cell2 surface receptors on the host cell membranes After being cleaved by a protease, PA binds to the two toxic enzymes, LF and EF, and mediates their transportation into the cytosol where they exert their pathogenic ef2 fects The structure of lethal factor the crucial pathogenic enzyme of anthrax toxin was described And the cloning of the human PA receptor using a genetic complementation approach was discussed As both PA and LF are possible targets for therapeutic agents, this review provides valuable information to researchers working towards better treatments for anthrax and tumor Key words anthrax toxin, lethal factor, protective antigen, anthrax toxin receptor, EF) (protective antigen, PA) LF 1 Zn 2 + MAPKK [1 6 ] ; EF 1 [7,8 ] ;PA, ] (LF) ; PA LF EF (PA), (ATR), ATR ATR cdna : ; : (No ) (No ) 3 :Tel : ,Fax : E2mail : edu cn [1 4 3 ] : (lethal factor, LF) (edema factor,,, Received :April 3,2002 ;Accepted :July 8,2002 Supported by National Natural Science Foundation of China (No ) and Natural Science Foundation of Guangdong Province (No ) 3 Corresponding author Tel : ,Fax : E2mail edu cn

2 6 : 665,PA LF EF 3,PA LF EF [9 ],EF 3, EF camp, [7 ] PA LF ] [10 ] 111 LF ] LF LF MAPKK 1 LF PA, LF ],LF 4 :, Zn 2 + PA ( ) ;, ( ) MAPKK22, MAPKK22 N 16 ( Fig 1) 3, 3, 12, PA ] ( ) Bacillus cereus VIP2 ( 1QS2), VIP2 NAD NAD Fig 1 Stereo ribbon representation of LF [11 13 ] Fig 2 Stereo representation of the active site centre of LF [14 ] II ] LF Zn ( ( Fig 2) LF ) 2 4 nm, (S1) 3, , LF Zn 2 +,, MAPKK22 N LF ]

3 S1, MAPKK21 MAPKK22 N S1 MAPKK N MAPKK MAPKK C MAPKK LF ] LF MAPKK N MAPK, MAPKK21 MAPKK22, [15 ], ] ; [16 ] 112 PA,17,18 ] PA 4, N 2 ATR PA ; PA, PA ; ;, [19,20 C, PA ] PA [18 20,PA ] :N PA 20 ( anthrax toxin receptor, ATR) C PA 63 PA 20,PA 63, PA LF EF PA 63 [ PA 63 ] 7 ( Fig 3) EF LF PA 20 PA 63 PA 63 LF EF [18 ] [ PA 63 ] 7 3 LF EF [9 ] EF 90 % LF [ PA 63 ] 7 ICR2191 ( DNA ph [ PA 63 ] 7, ) CHO2K1 [ PA 63 ] 7, PA LF N 2DTA LF N 2 [18 20 ] DTA LF N 255 R178 K197 R200 P205 I207 I210 K214 [18 PA LF EF ] [21 Mogridge ] PA 512 LF2PA2 PA 63 PA ( CHO2R1 1 CHO2R1 10) PA2D512K PA2K199EΠR468AΠ R470DPA, PA2D512K PA2K199EΠR468AΠ R470D LF N (LF N ) PA2D512K PA2K199EΠR468AΠR470D, Fig 3 Complex formation by wild type and oligomerization - de2 ficient mutants of PA 63 Only one potential pathway of formation of the ternary complex is illustrated [21 ] A( Von Willebrand factor type A, VWA),PA ATR [9 VWA ] ATR,Kenneth [19 ] [22 A ] CHO2K1 LF N 2DTA CHO2K1 CHO2R1 1, LF N 2DTA PA LF, PA2 DT Kenneth [19 ] D512K PA2K199EΠR468AΠR470D OGPA (Oregon Green conjugated form of PA,

4 6 : 667 OGPA) CHO2R1 1,, CHO2R1 1 ATR OGPA,T72ATR , PA 9 CHO2R1, OGPA ATR CHO2R111 VWAΠI CHO2R111 cdna 90 % CHO2R111 OGPA ATR cdna LF PA CHO2R111 CHO2R111 PA LF N 2DTA LF,Zn 2 + ATR cdna Zn 2 + LF, PA, [19 23 ] [17 ], [ PA 63 ] 7 ATR 44 PA 216 VWA VWA, ATR cdna ATR cdna [23 ] ATR 364 TEM8 cdna ATR C ATR C, TEM8,ATR, [19 25, TEM8 221 ] ATR, ATRΠTEM8,, Kenneth [19 ] PA ATR T7 ATR T72ATR PA PA EDTA,PA T72ATR ,, PA T72ATR ATR VWAΠI PA ATR CHO2K1 PA LF N 2DTA PA LF N 2DTA ATR , CHO2K1 Kenneth [19 ] CHO2K1 PA LF N 2DTA ATR ATR PA LF N 2DTA 80 nmolπl 500 nmolπl 50 % 100 %,ATR 3 LF ATR cdna,, PA,, ( References) 1 Mock M,Fouet A Anthrax Annu Rev Microbiol,2001,55 : Bhatnagar R,Batra S Anthrax toxin Crit Rev Microbiol,2001,27(3) : Brossier F,Mock M Toxins of Bacillus anthracis Toxicon,2001,39 (11) : Pannifer A D,Wong T Y,Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy D B, Collier R J, Park S, Leppla S H, Hanna P,

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