Protein & Cell

, Volume 4, Issue 3, pp 211–219 | Cite as

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

  • Yu-Chung Chang
  • Hao Zhang
  • Mark L. Brennan
  • Jinhua WuEmail author
Research Article


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.


Lamellipodin crystal structure RIAM coiled-coil oligomerization 

Supplementary material

13238_2013_2082_MOESM1_ESM.pdf (2.1 mb)
Supplementary material, approximately 2.10 MB.


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Copyright information

© Higher Education Press and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Yu-Chung Chang
    • 1
  • Hao Zhang
    • 1
  • Mark L. Brennan
    • 1
  • Jinhua Wu
    • 1
    Email author
  1. 1.Department of Developmental TherapeuticsFox Chase Cancer CenterPhiladelphiaUSA

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