Fig. 2. Inositide binding by FYVE and PX domains. (A) The Ins(1,3)P₂ (mimicking PtdIns(3)P) binding of the EEA1 FYVE domain occurs in a relatively shallow groove and involves the conserved R(R/K)HHCRxCG sequence. The binding pocket occupies the same position within the Hrs FYVE and Vps27p FYVE domains (red circle labeled 1). A hydrophobic tip facing the membrane is important for membrane penetration (blue arrows). The corresponding area within the PKC cysteine-rich domain (CRD) recognises the hydrophobic phorbol esters. (B) PX domains bind 3-phosphorylated inositides in the pocket formed by two helices and the loop connecting the ß1 and ß2 strand. An additional binding site that binds PA or other acidic phospholipids is located in the p47phox PX domain (red circle labeled 2). The long coil containing the PxxP consensus sequence (red) in many PX domains (only a single proline in the CISK PX domain) is the site of interaction with the SH3 domain in the p47phox PX domain. The PDB accession numbers used are: 1JOC, EEA1 FYVE (Dumas et al., 2001); 1DVP, Hrs FYVE (drosophila) (Mao et al., 2000); 1VFY, Vps27p FYVE (Misra and Hurley, 1999); 1PTR, PKC CRD (Zhang et al., 1995); 1H6H, p40^phox PX (Bravo et al., 2001); 1O7K, p47^phox PX (Karathanassis et al., 2002); 1OCU, Grd19p PX (Zhou et al., 2003); 1XTE, CISK PX (Xing et al., 2004).