Subunit structure of mature Mch4 and Mch5.
Truncated proMch5 (A) and proMch4 (C) lacking
most of the FADD-like prodomain (see schematics B and
D) were expressed in Escherichia coli,
purified to homogeneity, analyzed by SDS/PAGE and Coomassie
staining, and then microsequenced. (A) Lane 1, Total
bacterial lysate; lane 2, Ni2+-affinity purified mature
Mch5 enzyme. The N-terminal amino acid sequence of p11 is
LSSPQTRYIPDEADFLLGMA, and the N-terminal amino acid sequences of p18
are SPREQDSESQTLDKVYQMKS and SESQTLD KVYQMKS. (B) A
schematic diagram illustrating autoprocessing of proMch5. ProMch5 is
autocatalytically processed in two steps to generate the mature
p11/p18 enzyme complex. The first step involves processing at Asp-391
and Asp-401, which generates the p11 subunit and nonmature large
subunit. This form is enzymatically active and can autoprocess the
nonmature large subunit to the mature p18 species by cleavage at
Asp-227 and Asp-233 to remove the FADD-like prodomain. (C)
Lane 1, Ni2+-affinity purified mature Mch4 obtained after
expression of truncated proMch4 (V220-I479); lane 2,
Ni2+-affinity purified Mch4 obtained after expression of
truncated proMch4 (I194-I479). The N-terminal amino acid sequence of
p12 is ALNPEQAPTSLQDSIPAEAD, and the N-terminal amino acid sequence of
p17 is VKTFLEALPRA. The N-terminal amino acid sequence of p23 is
ASMTGGQQMGRDPIQIVTPP, which contains both the T7 tag
(underlined) and the proMch4 sequence. (D) A schematic
diagram illustrating autoprocessing of proMch4. Like proMch5, proMch4
undergoes autocatalytic processing in two steps to generate the mature
p12/p17 enzyme complex. The first step involves processing at
Asp-372, which generates the p12 subunit and nonmature large subunit
(in this case p23). The nonmature large subunit is autocatalytically
processed to the mature p17 species by cleavage at Asp-219 to remove
the FADD-like prodomain. Hatched boxes at the N and C termini of
truncated proMch4 or proMch5 represent the T7 and His6
tags, respectively. Lanes M in A and C
contain molecular weight markers.