PDBsum entry 4gn1

Signaling protein

PDB id: 4gn1

Contents

Protein chain

251 a.a.

Ligands

MLI ×4

Waters ×249

PDB id:

4gn1

Name:

Signaling protein

Title:

Crystal structure of the ra and ph domains of lamellipodin

Structure:

Ras-associated and pleckstrin homology domains-containing protein 1. Chain: a, b, c, d. Fragment: ra and ph domain (unp residues 266-520). Synonym: raph1, amyotrophic lateral sclerosis 2 chromosomal region candidate gene 18 protein, amyotrophic lateral sclerosis 2 chromosomal region candidate gene 9 protein, lamellipodin, proline- rich evh1 ligand 2, prel-2, protein rmo1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: raph1, als2cr18, als2cr9, kiaa1681, lpd, prel2, rmo1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.40Å R-factor: 0.256 R-free: 0.303

Authors:

Y.C.E.Chang,J.Wu

Key ref:

Y.C.Chang et al. (2013). Crystal structure of Lamellipodin implicates diverse functions in actin polymerization and Ras signaling. Protein Cell, 4, 211-219. PubMed id: 23483482 DOI: 10.1007/s13238-013-2082-5

Date:

16-Aug-12 Release date: 28-Nov-12

Protein chains

Q70E73  (RAPH1_HUMAN) -  Ras-associated and pleckstrin homology domains-containing protein 1 from Homo sapiens

Seq: 1250 a.a.

Struc: 251 a.a.

DOI no: 10.1007/s13238-013-2082-5

Protein Cell 4:211-219 (2013)

PubMed id: 23483482

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

Y.C.Chang, H.Zhang, M.L.Brennan, J.Wu.

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.