CALM ANTH domain, belongs to a family of conserved N-terminal domains (conserved from yeast to man) which bind to PtdIns(4,5)P2 in membranes. There is greater than 50% amino acid identity in this domain between rat-AP180, C-elegans (UNC-11) and Drosophila (LAP)

ANTH structure
AP180 N-Terminal Homology domain

The AP180 family from yeast to man has a conserved N-terminal domain we crystallised and for the first time showed that this domain is a PtdIns(4,5)P₂ binding domain. There is greater than 50% amino acid identity in this domain between rat, C-elegans (UNC-11) and Drosophila (LAP).

AP180 homologues have ANTH domains followed by motif domains that contain DxF, NPF and clathrin-binding motifs

We solved the structure of AP180-2/CALM ANTH domain. The structure is a solenoid of 9 helices. The PtdIns(4,5)P₂ binding residues are spread over several helices and has the conserved sequence Kx₉Kx(K/R)(H/Y). An ANTH domain is also found in HIP1 and HIP1R and the PtdIns(4,5)P₂ binding sequence is conserved.

Structure of CALM ANTH domain bound to PIP2 lipid headgroup

CALM ANTH domain and GGA VHS domain superposition

AP180 and LAP ANTH domain ssuperpositions

see Epsin ENTH structure

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