plasma membrane extracellular cytoplasm space 723 - WKLLITIHDRKEF- COOH - WKVGFFKRNRP- -соон COOH 995 Figure Q19-3 Schematic representation of Cbb3 integrin (Problem 19-10). The D723 and R995 residues are indicated. (From P.E. Hughes et al., J. Biol. Chem. 271:6571-6574, 1996. With permission from American Society for Biochemistry and Molecular Biology.)

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Chapter1: The Human Body: An Orientation
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The affinity of integrins for matrix components can
be modulated by changes to their cytoplasmic domains:
a process known as inside-out signaling. You have iden-
tified a key region in the cytoplasmic domains of αIIbβ3
integrin that seems to be required for inside-out signaling
(Figure Q19–3). Substitution of alanine for either D723
in the β chain or R995 in the α chain leads to a high level
of spontaneous activation, under conditions where the
wild-type chains are inactive. Your advisor suggests that
you convert the aspartate in the β chain to an arginine
(D723R) and the arginine in the α chain to an aspartate
(R995D). You compare all three α chains (R995, R995A,
and R995D) against all three β chains (D723, D723A, and
D723R). You find that all pairs have a high level of sponta-
neous activation, except D723 vs R995 (the wild type) and
D723R vs R995D, which have low levels. Based on these
results, how do you think the αIIbβ3 integrin is held in its
inactive state?

plasma
membrane
extracellular
cytoplasm
space
723
- WKLLITIHDRKEF-
COOH
- WKVGFFKRNRP-
-соон
COOH
995
Figure Q19-3 Schematic representation of Cbb3 integrin
(Problem 19-10). The D723 and R995 residues are indicated.
(From P.E. Hughes et al., J. Biol. Chem. 271:6571-6574, 1996.
With permission from American Society for Biochemistry and
Molecular Biology.)
Transcribed Image Text:plasma membrane extracellular cytoplasm space 723 - WKLLITIHDRKEF- COOH - WKVGFFKRNRP- -соон COOH 995 Figure Q19-3 Schematic representation of Cbb3 integrin (Problem 19-10). The D723 and R995 residues are indicated. (From P.E. Hughes et al., J. Biol. Chem. 271:6571-6574, 1996. With permission from American Society for Biochemistry and Molecular Biology.)
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