Pleckstrin homology domain

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Federal government websites often end in. The site is secure. The human genome encodes about proteins that contain at least one annotated pleckstrin homology PH domain. As the first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes. PH domains constitute one of the largest protein superfamilies, and have diverged to regulate many different signaling proteins and modules such as Dbl homology DH and Tec homology TH domains. The ligands of approximately 70 PH domains have been validated by binding assays and complexed structures, allowing meaningful extrapolation across the entire superfamily. In addition to the linear sequence motifs which are employed for phosphoinositide recognition, the three dimensional structural features that allow peripheral membrane domains to approach and insert into the bilayer are pinpointed and can be predicted ab initio.

Pleckstrin homology domain

Letunic et al. Pleckstrin homology PH domains are small modular domains that occur in a large variety of proteins. Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. PH domains have been found to possess inserted domains such as in PLC gamma, syntrophins and to be inserted within other domains. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids. All known cases have a common structure consisting of two perpendicular anti-parallel beta sheets, followed by a C-terminal amphipathic helix. The loops connecting the beta-strands differ greatly in length, making the PH domain relatively difficult to detect. There are no totally invariant residues within the PH domain. This tree includes only several representative species. The complete taxonomic breakdown of all proteins with PH domain is also avaliable. Click on the protein counts, or double click on taxonomic names to display all proteins containing PH domain in the selected taxonomic class.

Mayer B. Cell Rep.

Pleckstrin homology domain PH domain or PHIP is a protein domain of approximately amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton. Individual PH domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring, e. This is important because it makes the recruitment of different PH domain containing proteins sensitive to the activities of enzymes that either phosphorylate or dephosphorylate these sites on the inositol ring, such as phosphoinositide 3-kinase or PTEN , respectively. Thus, such enzymes exert a part of their effect on cell function by modulating the localization of downstream signaling proteins that possess PH domains that are capable of binding their phospholipid products. The 3D structure of several PH domains has been determined. The loops connecting the beta-strands differ greatly in length, making the PH domain relatively difficult to detect while providing the source of the domain's specificity. The only conserved residue among PH domains is a single tryptophan located within the alpha helix that serves to nucleate the core of the domain.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Here we employ a single-molecule pulldown assay to study interactions of lipid vesicles with full-length proteins in mammalian whole cell lysates. Twenty predicted binders and 11 predicted non-binders are assayed, yielding results highly consistent with the prediction. Taken together, our findings reveal unexpected lipid-binding specificity of PH domain-containing proteins. Mintu Chandra, Yanni K. Chin, … Brett M.

Pleckstrin homology domain

Federal government websites often end in. The site is secure. Pleckstrin-2 is a member of pleckstrin family with well-defined structural features that was first identified in

Pgstats

PMC PMC Copyright notice. Domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Individual PH domains possess specificities for phosphoinositides phosphorylated at different sites within the inositol ring, e. Genome-Wide Analysis of Membrane Binding of PH Domains The membrane interactions of 69 human PH domains and 19 mammalian orthologues were analyzed using available structural and experimental data. Through the following examples, we inspect the consistency of predictions of membrane binding across the family. Figure 1. When protein complexes or multimeric proteins were found, only the structure corresponding to the PH domain was analyzed. Cell 13 , — SiMPull data for the proteins in bold are shown in c.

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Similarly, of the 49 domains found to interact with membranes experimentally, 36 were confirmed by MODA predictions. Farp2 and Stk25 are candidate genes for the HDL cholesterol locus on mouse chromosome 1. Narayan, K. All known FYVE domains select this phosphoinositide. Skip to main content Thank you for visiting nature. Our findings reveal unexpected lipid binding specificity and suggest that PIP recognition by PH domain-containing proteins is more prevalent than previously believed. For proteins containing several PH domains, each PH domain is numbered according to its relative position within the protein. The structure of the PH domain is similar to those published previously: a seven-stranded bent beta-sheet with a C-terminal alpha-helix. Structure of the Rho-specific guanine nucleotide-exchange factor Xpln. At the base of this channel is a residue segment of which has been implicated in the binding of to protein kinase C. The absence of MODA patch correlates the observations. Single copies of an approximately residue domain are shown to be present in the sequences of 14 eukaryotic proteins, including yeast byr2, STE11, ste4, and STE50, which are essential participants in sexual differentiation. Huang P.