Pleckstrin homology domain

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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.

Pleckstrin homology domain

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. A large number of PH domains have poor affinity for phosphoinositides and are hypothesized to function as protein binding domains. A Genome-wide look in Saccharomyces cerevisiae showed that most of the 33 yeast PH domains are indeed promiscuous in binding to phosphoinositides, while only one Num1-PH behaved highly specific. Contents move to sidebar hide. Article Talk. Read Edit View history.

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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.

Federal government websites often end in. The site is secure. Pleckstrin homology PH domains represent the 11 th most common domain in the human proteome. Cases in which PH domains bind specific phosphoinositides with high affinity are restricted to those phosphoinositides that have a pair of adjacent phosphates in their inositol headgroup. One group of PH domains appears to bind both phosphoinositides with little specificity and Arf family small G-proteins, and are targeted to the Golgi apparatus where both phosphoinositides and the relevant Arfs are both present. Here, the PH domains may function as coincidence detectors.

Pleckstrin homology 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. Daniel R.

Dasha daley

Figure 1. Contents move to sidebar hide. Given the small number of such negative test cases, we investigated two proteins further. One group of PH domains appears to bind both phosphoinositides with little specificity and Arf family small G-proteins, and are targeted to the Golgi apparatus where both phosphoinositides and the relevant Arfs are both present. Tong Y. Through the following examples, we inspect the consistency of predictions of membrane binding across the family. This aspect of the motif was found in only one or two examples that did not bind strongly to phosphoinositides in our yeast study. Patch Finder Plus PFplus : a web server for extracting and displaying positive electrostatic patches on protein surfaces. This suggests that despite the evolutionary changes, sections of the protein sequence have been maintained for functional purposes. By contrast with PH domains, FYVE domains bind much more strongly to their target lipid in membranes than to the isolated inositol phosphate headgroup [ 46 ]. Protein kinase C conserved region 1 C1 domains Cysteine-rich domains. Moreover there is generally little appetite for publishing negative results. A large number of PH domains have poor affinity for phosphoinositides and are hypothesized to function as protein binding domains. Structure and phosphatidylinositol- 3,4 -bisphosphate binding of the C-terminal PH domain of human pleckstrin.

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Tanaka K et al. Harlan, J. Our yeast studies showed that only six additional PH domains from Boi1p, Boi2p, Cla4p, Osh1p, Osh2p, and Skm1p possess reasonably strong phosphoinositide binding in vitro. Copy to clipboard. The E. Barnett S. Currie R. These proteins are thought to function as nuclear receptors for this phosphoinositide. In these cases, binding of the PH domain to its protein target may resemble that seen for well described protein-protein interactions driven by modules such as PTB and EVH domains that share the PH domain fold [ 21 , 73 ]. The structure consists of an up-and-down beta-barrel of seven antiparallel beta-strands and a C-terminal amphiphilic alpha-helix that caps one end of the barrel. Conclusions Since their identification in , the broad family of PH domains and structural relatives has burgeoned.