Protein & Cell

, Volume 4, Issue 3, pp 211–219

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

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

DOI: 10.1007/s13238-013-2082-5

Cite this article as:
Chang, YC., Zhang, H., Brennan, M.L. et al. Protein Cell (2013) 4: 211. doi:10.1007/s13238-013-2082-5

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.

Keywords

Lamellipodin crystal structure RIAM coiled-coil oligomerization 

Supplementary material

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

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
  1. 1.Department of Developmental TherapeuticsFox Chase Cancer CenterPhiladelphiaUSA

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