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Viewing report
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Diversity in Molecular Recognition of Phospholipids
by PH Domains. Edition No. 1
VDM Publishing House, Sep 2008, Pages: 224
Phospholipid-binding domains are key components of
signaling pathways that normally drive membrane
recruitment of their host protein in vivo. The most
numerous Pleckstrin Homology (PH) domains are
commonly associated with high affinity,
phosphoinositide (PPIns)-specific binding in vitro
and membrane-specific targeting in vivo. In fact, the
majority of PH domains bind PPIns promiscuously and
with low affinity in vitro and are diffusely
localized in vivo. A novel class of PH domains -
belonging to the OSBP/FAPP family - is identified
here with distinct phospholipid-binding properties,
having both promiscuous and high affinity for PPIns
in vitro. Additionally, the crystal structure of a
member of this class - Osh1p PH - has been determined
at high resolution. The PPIns-binding properties of
another unusual PH domain, belonging to SH3BP2, is
also discussed, which has implications in the spatial
and temporal regulation of 3-phosphoinositides.
Finally, an alkylphospholipid drug is identified that
interacts directly with the PH domain of
Akt1/PKBalpha in vitro, which has implications in the
use of PH domains as possible targets for therapeutic
drug intervention.
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