244
Annexins
2
Structure and Mechanism of Action
The annexins, in general, have proven to be
relatively easy to isolate in high purity, and
this advantage has led to several success-
ful attempts to crystallize members of the
family. The structure of annexin V reveals
that each of the four 70–amino acid re-
peats forms a compact bundle of
α
-helices
and these four bundles are arranged in a
plane (Fig. 2). Viewed from the side, the
molecule displays a convex face, thought to
be the membrane-binding face, and a con-
cave face, thought to face the cytoplasm.
Each homologous domain forms one or
two potential calcium binding sites, which
are complex in that they involve convergent
loops from different parts of the domain.
In addition, the positions of sulfate ions in
the loops (derived from the crystallization
medium) suggest that the phosphate of a
lipid head group may also sit in the bind-
ing pocket and coordinate the calcium ion.
This geometry would explain the interde-
pendence of calcium and lipid binding by
the annexins. Since all the lipid binding
sites of the annexin core domains face a
single membrane, they may be able to in-
tegrate information about membrane-lipid
composition. In general, all the annexins
bind with higher af±nity (i.e. at lower lev-
els of calcium) to acidic phospholipids.
However, there is some variation reported
in the literature for different annexins
with regard to order of preference for
(a)
(b)
Fig. 2
Ribbon plots of the structure of
annexin V as determined by X-ray
diffraction. (a) ‘‘Side’’ view of the
molecule, with the calcium binding sites
and the membrane-binding face at the
top. Calcium ions are represented by the
spheres. The high-afFnity sites are
represented by the Frst, second, and
Ffth spheres from left to right; the third
and fourth spheres indicate low-afFnity
ion binding sites that were identiFed by
lanthanide binding. The extended
N-terminus is seen at the bottom.
(b) View of the ‘‘cytoplasmic’’ side of
themo
lecu
leandtheN-terminus.The
calcium binding sites are on the
opposite face. Note the potential
channel structure in the center of the
molecule. [±rom Creutz (1992), with
permission. Original Fgure kindly
provided by A. Burger and R. Huber.]
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