Selectivity Determinants of RHO GTPase Binding to IQGAPs.
Int J Mol Sci
; 22(22)2021 Nov 22.
Article
em En
| MEDLINE
| ID: mdl-34830479
ABSTRACT
IQ motif-containing GTPase-activating proteins (IQGAPs) modulate a wide range of cellular processes by acting as scaffolds and driving protein components into distinct signaling networks. Their functional states have been proposed to be controlled by members of the RHO family of GTPases, among other regulators. In this study, we show that IQGAP1 and IQGAP2 can associate with CDC42 and RAC1-like proteins but not with RIF, RHOD, or RHO-like proteins, including RHOA. This seems to be based on the distribution of charged surface residues, which varies significantly among RHO GTPases despite their high sequence homology. Although effector proteins bind first to the highly flexible switch regions of RHO GTPases, additional contacts outside are required for effector activation. Sequence alignment and structural, mutational, and competitive biochemical analyses revealed that RHO GTPases possess paralog-specific residues outside the two highly conserved switch regions that essentially determine the selectivity of RHO GTPase binding to IQGAPs. Amino acid substitution of these specific residues in RHOA to the corresponding residues in RAC1 resulted in RHOA association with IQGAP1. Thus, electrostatics most likely plays a decisive role in these interactions.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ligação Proteica
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Proteína cdc42 de Ligação ao GTP
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Proteína rhoA de Ligação ao GTP
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Proteínas Ativadoras de ras GTPase
Limite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2021
Tipo de documento:
Article