, 2006 ; Schubot et al., 2005 ; Singer et al., 2004 ; Phan et al., 2004 ; Evdokimov et al., 2002 ; Stebbins & Gal锟斤拷n, 2001b ; Vogelaar et al., 2010 ). YopH is a 468-amino-acid protein that is injected into host cells by the T3SS of several species of the Yersinia genus, including Y. pestis, the causative agent of bubonic and pneumonic plague (Guan & Dixon, 1990 ; Bliska et al., 1991 ). The C--terminal portion of the effector (spanning residues ~160锟紺468) functions as a protein tyrosine phosphatase (PTP) in the host cell, altering signal transduction pathways (Rosqvist et al., 1988 ; Andersson et al., 1996 , 1999 ; Bartra et al., 2001 ; Black & Bliska, 1997 ; Black et al., 2000 ; Deleuil et al., 2003 ; Green et al., 1995 ; Hamid et al., 1999 ). The N-terminal region of the polypeptide has two functions: in the bacterium residues 1锟紺130 bind to the SycH chaperone and are required for translocation into the host cell through the T3SS, whereas in the host cell this domain aids in targeting the PTP domain to its proper substrates (Woestyn et al., 1996 ; Black et al., 1998 ; Evdokimov et al., 2001 ; Montagna et al., 2001 ; Smith et al., 2001 ; Khandelwal et al., 2002 ). An important question both from a biochemical/structural aspect as well as in general considerations of the host锟紺pathogen interaction and evolutionary biology is whether this 锟斤拷reuse锟斤拷 of the polypeptide in two different physiological environments is associated with dual structure锟紺function states. In other words, does the polypeptide 1锟紺130 of YopH adopt different folds in the bacterial versus the host environment that are associated with these different functions? The initial evidence would point to the dual structure锟紺function possibility as the most likely hypothesis. YopH(1锟紺130) is known to form a globular stable fold on its own, and this fold has been probed through structure-based mutagenesis to test the function of surface-exposed residues in the host cell, indicating that this domain as folded in the crystal structures is likely to be the functional form of the molecule in the host (Evdokimov et al., 2001 ; Smith et al., 2001 ; Khandelwal et al., 2002 ). However, all previous chaperone锟紺effector studies from multiple T3SSs, including the related structure of the YopH chaperone SycH with the regulatory molecule YscM2 (which contains significant homology to YopH in its N--terminal domain), have shown that the interaction consists of a nonglobular polypeptide in the effector (Lilic et al., 2006 ; Schubot et al., 2005 ; Singer et al., 2004 ; Phan et al., 2004 ; Evdokimov et al., 2002 ; Stebbins & Gal锟斤拷n, 2001b ; Vogelaar et al., 2010).
Four Great Tactics For Amuvatinib
Four Great Tactics For Amuvatinib