TY - JOUR
T1 - Intramolecular dimerization is required for the chlamydia-secreted protease CPAF to degrade host transcriptional factors
AU - Dong, Feng
AU - Sharma, Jyotika
AU - Xiao, Yanming
AU - Zhong, Youmin
AU - Zhong, Guangming
PY - 2004/7
Y1 - 2004/7
N2 - We previously identified a chlamydial protein designated CPAF (chlamydia protease/proteasome-like activity factor) that is secreted into host cell cytosol for degrading host transcription factors required for major histocompatibility complex antigen expression. Here we report that CPAF, synthesized as a 70-kDa proprotein, is processed into two fragments (designated CPAFn and CPAFc) to form intramolecular dimers that are much more stable than the naïve CPAF. Precipitation with antibodies that recognized CPAF dimers removed the proteolytic activity responsible for degrading host transcription factor RFX5 from chlamydia-infected host cell cytosol, while precipitation with antibodies that recognized free CPAF fragments alone did not remove this activity. Separation of CPAFn from CPAFc resulted in a loss of proteolytic activity. Furthermore, neither expressed full-length CPAF that was not processed nor coexpressed CPAFn and CPAFc fragments that failed to form dimers degraded RFX5. These observations demonstrate that intramolecular dimerization is required for CPAF to degrade host transcription factors, a strategy that is utilized by an obligate intracellular bacterial species to evade host defenses.
AB - We previously identified a chlamydial protein designated CPAF (chlamydia protease/proteasome-like activity factor) that is secreted into host cell cytosol for degrading host transcription factors required for major histocompatibility complex antigen expression. Here we report that CPAF, synthesized as a 70-kDa proprotein, is processed into two fragments (designated CPAFn and CPAFc) to form intramolecular dimers that are much more stable than the naïve CPAF. Precipitation with antibodies that recognized CPAF dimers removed the proteolytic activity responsible for degrading host transcription factor RFX5 from chlamydia-infected host cell cytosol, while precipitation with antibodies that recognized free CPAF fragments alone did not remove this activity. Separation of CPAFn from CPAFc resulted in a loss of proteolytic activity. Furthermore, neither expressed full-length CPAF that was not processed nor coexpressed CPAFn and CPAFc fragments that failed to form dimers degraded RFX5. These observations demonstrate that intramolecular dimerization is required for CPAF to degrade host transcription factors, a strategy that is utilized by an obligate intracellular bacterial species to evade host defenses.
UR - http://www.scopus.com/inward/record.url?scp=3042643366&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042643366&partnerID=8YFLogxK
U2 - 10.1128/IAI.72.7.3869-3875.2004
DO - 10.1128/IAI.72.7.3869-3875.2004
M3 - Article
C2 - 15213129
AN - SCOPUS:3042643366
SN - 0019-9567
VL - 72
SP - 3869
EP - 3875
JO - Infection and immunity
JF - Infection and immunity
IS - 7
ER -