Crystal structure of Lamellipodin implicates diverse functions in actin polymerization and Ras signaling
Protein & Cell
;
(12): 211-219, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-757820
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosfatidilinositóis
/
Ligação Proteica
/
Sítios de Ligação
/
Proteínas Recombinantes
/
Dados de Sequência Molecular
/
Transdução de Sinais
/
Proteínas de Transporte
/
Química
/
Mutagênese
/
Actinas
Limite:
Humanos
Idioma:
Inglês
Revista:
Protein & Cell
Ano de publicação:
2013
Tipo de documento:
Artigo
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