4GN1

Crystal Structure of the RA and PH domains of Lamellipodin

Summary for 4GN1

• Entry DOI: 10.2210/pdb4gn1/pdb
• Related: 4GMV
• Descriptor: Ras-associated and pleckstrin homology domains-containing protein 1, MALONATE ION (3 entities in total)
• Functional Keywords: ra-ph, coiled-coil region, ras-association domain, pleckstrin homology domain, cytoskeletal protein, ena/vasp binding, cell migration, cell adhesion, signaling protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Peripheral membrane protein; Cytoplasmic side: Q70E73
• Total number of polymer chains: 4
• Total formula weight: 121420.04

Authors

Chang, Y.C.E.,Wu, J. (deposition date: 2012-08-16, release date: 2012-11-28, Last modification date: 2023-09-13)

Primary citation

Chang, Y.C.,Zhang, H.,Brennan, M.L.,Wu, J.
Crystal structure of Lamellipodin implicates diverse functions in actin polymerization and Ras signaling.
Protein Cell, 4:211-219, 2013

PubMed 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.

PubMed: 23483482
DOI: 10.1007/s13238-013-2082-5

Experimental method

X-RAY DIFFRACTION (2.4 Å)