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. 2013 Mar 13;4(3):211–219. doi: 10.1007/s13238-013-2082-5

Crystal structure of Lamellipodin implicates diverse functions in actin polymerization and Ras signaling

Yu-Chung Chang 1, Hao Zhang 1, Mark L Brennan 1, Jinhua Wu 1,✉
PMCID: PMC4875499  PMID: 23483482

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.

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-013-2082-5 and is accessible for authorized users.

Keywords: Lamellipodin, crystal structure, RIAM, coiled-coil, oligomerization

Electronic supplementary material

13238_2013_2082_MOESM1_ESM.pdf (2.1MB, pdf)

Supplementary material, approximately 2.10 MB.

Footnotes

Electronic Supplementary Material

Supplementary material is available for this article at 10.1007/s13238-013-2082-5 and is accessible for authorized users.

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Supplementary Materials

13238_2013_2082_MOESM1_ESM.pdf (2.1MB, pdf)

Supplementary material, approximately 2.10 MB.

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