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PDBsum entry 4gn1
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Signaling protein
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PDB id
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4gn1
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References listed in PDB file
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Key reference
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Title
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Crystal structure of lamellipodin implicates diverse functions in actin polymerization and ras signaling.
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Authors
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Y.C.Chang,
H.Zhang,
M.L.Brennan,
J.Wu.
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Ref.
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Protein Cell, 2013,
4,
211-219.
[DOI no: ]
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PubMed id
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Abstract
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The adapter protein Lamellipodin (Lpd) plays an important role in cell
migration. In particular, Lpd mediates lamellipodia formation by regulating
actin dynamics via interacting with Ena/VASP proteins. Its RA-PH tandem domain
configuration suggests that like its paralog RIAM, Lpd may also mediate
particular Ras GTPase signaling. We determined the crystal structures of the Lpd
RA-PH domains alone and with an N-terminal coiled-coil region (cc-RA-PH). These
structures reveal that apart from the anticipated coiled-coil interaction, Lpd
may also oligomerize through a second intermolecular contact site. We then
validated both oligomerization interfaces in solution by mutagenesis. A
fluorescence-polarization study demonstrated that Lpd binds phosphoinositol with
low affinity. Based on our crystallographic and biochemical data, we propose
that Lpd and RIAM serve diverse functions: Lpd plays a predominant role in
regulating actin polymerization, and its function in mediating Ras GTPase
signaling is largely suppressed compared to RIAM.
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