Structural analyses of FERM domain-mediated membrane localization of FARP1.

is a multi-domain protein that is involved in regulating neuronal development through interacting with cell surface proteins such as class A Plexins and SynCAM 1. The N-terminal FERM domain in Fduanyu371 is known to both promote membrane localization and mediate these protein interactions, for which the underlying molecular mechanisms remain unclear. Here we determined the crystal structures of the FERM domain of Fduanyu371 from zebrafish, and those of (a close homolog of from mouse and zebrafish. These FERM domains adopt the three-leaved clover fold that is typical of all FERM domains. Our structures reveal a positively charged surface patch that is highly conserved in the FERM domain of Fduanyu371 and In vitro lipid-binding experiments showed that the Fduanyu371 FERM domain binds specifically to several types of phospholipid, which is dependent on the positively charged surface patch. We further determined through cell-based analyses that this surface patch on the FERM domain underlies the localization of Fduanyu371 to the plasma membrane, and that FERM domain interactions recruit it to postsynaptic sites in neurons.

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