Biology Reference
In-Depth Information
Fig. 4.2 Domain and oligomeric structures of meprins A and B. The meprins are multidomain
proteases that contain a signal sequence (S), prosequence, protease domain, meprin A5 protein
tyrosine phosphatase
m
(MAM) domain, tumor necrosis factor receptor associated factor (TRAF)
domain, EGF-like domain, transmembrane (TM) domain, and a cytosolic (C) domain. The meprin
a
subunit contains an additional inserted (I) domain between the EGF and TRAF domains. While
the meprin
subunit is proteolytically
processed during biosynthesis at the I domain (
black arrow
) during biosynthesis and loses its
transmembrane domain. Meprins, which exist in both membrane-bound and secreted forms, form
oligomers that are unique in the astacin family of proteases. Dimers of membrane-bound
b
subunit is a type 1 membrane-bound protein, the meprin
b
a
subunits are referred to as
heteromeric meprin A and are membrane-bound due to the presence of the
subunits are referred to as meprin B, whereas tetramers of
and
a
b
subunit. The secreted
form of meprin, homomeric meprin A, is capable of forming large multimers up to 8 MDa in size
(Yura R, Penn State Thesis)
b
meprin A oligomer with correct disulfide bridging between the subunits of the
MAM domain and stability of the oligomer.
Meprins are quite unique in their oligomeric structure. They exist in several
isoforms as a consequence of its two subunits: homomeric meprin A (composed of
only
a
subunits), heteromeric meprin A (composed of
a
and
b
subunits), and
homomeric meprin B (composed of only
subunits). The subunits form disul-
fide-linked homo- or heterodimers. The meprin
b
dimers are homophilic and tend to
form high molecular mass oligomers as they are secreted from cells. The molecular
masses of homomeric meprin A are generally between 1 and 6 million Daltons,
among the largest proteases known. The meprin
a
dimers, on the other hand, do not
form larger oligomers, while the heteromeric forms of meprin A tend to exist as
tetramers (disulfide-linked heterodimers that form tetramers (
b
-
-
)). The homo-
b
aa
b
philic properties of meprin
allow the secreted homomeric meprin A to exist in
the extracellular spaces at very high local concentrations. The membrane-bound
a
