74
4 Interaction Between the L3-2 Loop and the Near
N-Terminal Region
Reflecting the pH dependency of the interaction between chromogranins and the
IP 3 Rs, chromogranin A bound the L3-2 loop of the IP 3 R only at the intragranular
pH 5.5, but not at pH 7.5. However chromogranin B bound the L3-2 loop of the IP 3 R
at both pH 5.5 and 7.5, although the interaction at pH 7.5 was considerably weaker
than that at pH 5.5. Moreover, it was further shown that tetrameric chromogranins
interact with four molecules of L3-2 at pH 5.5 (Yoo and Lewis 1995 ) (Fig. 2 ). The
chromogranin region that interacted with the L3-2 loop of the IP 3 R was shown to be
the conserved near N-terminal regions of both CGA and CGB. As was the case with
intact CGA, the near N-terminal region of CGA also interacted with the L3-2 loop
of the IP 3 R only at pH 5.5, but dissociated completely from each other at near physi-
ological pH 7.5. However, the near N-terminal region of CGB still interacted with
the L3-2 loop even at pH 7.5, as was the case with intact CGB.
Although the conserved near N-terminal region of chromogranins is shown to
interact with the L3-2 loop of the IP 3 Rs, the interaction strength of whole chromo-
granins for the L3-2 loop is at least two orders of magnitude higher than that of the
near N-terminal region for the L3-2 loop (Table 3 ). The interaction strength between
Fig. 2 Schematic model
showing the coupling
between the tetrameric
IP 3 Rs and tetrameric
chromogranins.
Heterotetrameric IP 3 R/Ca2+
channel and CGA 2 CGB 2
heterotetrameric
chromogranins are coupled
through the L3-2 loops of
IP 3 Rs and the near
N-terminal regions of
chromogranins A and B
S. H. Yo o