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Chang YC , Zhang H , Brennan ML , Wu J
Crystal structure of Lamellipodin implicates diverse functions in actin polymerization and Ras signaling
Protein Cell. 2013 Mar;4(3) :211-9
PMID: 23483482   
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Abstract
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.
Notes
Chang, Yu-Chung Zhang, Hao Brennan, Mark L Wu, Jinhua Germany Protein Cell. 2013 Mar;4(3):211-9. doi: 10.1007/s13238-013-2082-5. Epub 2013 Mar 13.