Calcium Biochemistry
145
site each contain a pair of EF-hands, and
the domains are connected by a long
central helix providing a dumbbell-shaped
appearance as revealed by crystal-structure
determination. The N- and C-terminal
domains bind calcium cooperatively, the
C-terminal domain with higher af±nity.
Recent multinuclear magnetic resonance
experiments of the Ca
2
+
-bound form
of calmodulin corroborated the general
validity of the dumbbell-shaped structure
in solution, but indicated the high degree
of flexibility of the central part of the
helix that is also supported by a high B-
factor (temperature-factor) in that region
in the crystal structure. This flexibility
in the center of the molecule is an
important property for the interaction with
targets. Upon binding of calcium and
subsequent conformational change of the
protein, the extended dumbbell-shaped
form of calmodulin in the absence of a
target is transformed into a more compact
form upon interacting with a target. By
bending the central helix and bringing
the two domains close together, thereby
engul±ng the peptide representing the
CaM binding domain is documented by
numerous examples, some of which will be
discussed below in more detail (see Fig. 2).
(a) CaM
(b) CaM/C20W
(c) CaM/M13
Fig. 2
Surface representation of calcium-bound
calmodulin (CaM) and its different binding
modes to peptides. The N-terminal half of CaM
is in orange, the C-terminal half is in red, and the
peptides are in blue. The orientation of the
C-terminal half of CaM is the same in all cases.
(a) Crystal structure of calcium-bound CaM. (b)
Solution structure of the CaM/C20W complex
showing that the peptide C20W, corresponding
to the N-terminal portion of the CaM binding
domain of the plasma membrane Ca
2
+
pump,
but lacking the C-terminal hydrophobic anchor
residue, binds only to the C-terminal half of
CaM. (c) The solution structure of CaM/M13
shows a compact globular complex involving
both C- and N-terminal halves of CaM in binding
the peptide M13 corresponding to the CaM
binding domain of MLCK. (Reprinted with
permission from Elshorst et al., 1999,
Biochemistry
,
38
, 12320–12332).
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