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Structural basis for NHERF recognition by ERM proteins.

Shin-ichi Terawaki·Ryoko Maesaki·Toshio Hakoshima
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Abstract

The Na+/H+ exchanger regulatory factor (NHERF) is a key adaptor protein involved in the anchoring of ion channels and receptors to the actin cytoskeleton through binding to ERM (ezrin/radixin/moesin) proteins. NHERF binds the FERM domain of ERM proteins, although NHERF has no signature Motif-1 sequence for FERM binding found in adhesion molecules. The crystal structures of the radixin FERM domain complexed with the NHERF-1 and NHERF-2 C-terminal peptides revealed a peptide binding site of the FERM domain specific for the 13 residue motif MDWxxxxx(L/I)Fxx(L/F) (Motif-2), which is distinct from Motif-1. This Motif-2 forms an amphipathic alpha helix for hydrophobic docking to subdomain C of the FERM domain. This docking causes induced-fit conformational changes in subdomain C and affects binding to adhesion molecule peptides, while the two binding sites are not overlapped. Our studies provide structural paradigms for versatile ERM linkages between membrane proteins and the cytoskeleton.

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Amino Acid MotifsAmino Acid SequenceAnimalsAntigens, CDBinding SitesCell Adhesion MoleculesCytoskeletonDNA-Binding ProteinsHumansKineticsMiceModels, MolecularMolecular ConformationMolecular Sequence DataPeptidesPhosphoproteinsProtein BindingProtein ConformationProtein Structure, SecondaryProtein Structure, TertiarySequence Homology, Amino AcidSodium-Hydrogen ExchangersStatic ElectricityTime FactorsTranscription FactorsJournal ArticleResearch Support, Non-U.S. Gov't

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Shin-ichi Terawaki, Ryoko Maesaki, Toshio Hakoshima. 2006. Structural basis for NHERF recognition by ERM proteins.. https://doi.org/10.1016/j.str.2006.01.015

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