Pleckstrin homology domain

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 pleckstrin homology domain first phosphoinositide binding module domain to be discovered, the PH domain recruits diverse protein architectures to cellular membranes.

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

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.

Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling pleckstrin homology domain to interact with other components of the signal transduction pathways. Thomas F. Email address Sign up.

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.

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.

Pleckstrin homology domain

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. A central challenge in understanding the majority of PH domains to establish whether the very low affinity phosphoinositide binding reported in many cases has any functional relevance.

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Phosphatidylinositol-specific phospholipase C Y domain. Rossman, K. Biochim Biophys Acta. We report here the crystal structure of the human T-cell isoform tau dimer at 2. 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 ]. Binding was observed for all with both types of vesicles. Yu, J. Rather, the availability of a 3D structure-based predictive tool such as MODA, which is available at moda. Takegahara N. However, it remains possible that it is a red herring in many cases, and the role played by weak phosphoinositide binding needs to be considered on a case-by-case basis for this functionally heterogeneous domain family. Due to overexpression of the EGFP-fusion proteins it is unlikely that any endogenous proteins in the lysate would reach stoichiometric levels to contribute directly to the observed recombinant protein binding to lipid vesicles. Supplementary Data 3. Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology PH domain of tandem PH-domain-containing protein 1 TAPP1 : Molecular basis of lipid specificity.

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Liu H. View author publications. The interactions of peripheral proteins with membranes range over a wide spectrum of affinities ranging from nM to mM. All cDNAs in the final plasmids were sequence-confirmed in their entirety. Each monomer Mr 28K is composed of an unusual arrangement of nine antiparallel alpha-helices organized as two structural domains. To test this hypothesis, structural studies of one or more of these PH domains is required, bound to a series of different headgroups. An amino acid was scored in the probability matrix if it was found in at least one PH domain in the group. Using electrostatics and varying levels of head-group specificity, PH domains may localize and orient signaling proteins, providing a general membrane targeting and regulatory function. Due to overexpression of the EGFP-fusion proteins it is unlikely that any endogenous proteins in the lysate would reach stoichiometric levels to contribute directly to the observed recombinant protein binding to lipid vesicles. Ferguson K. All lipids were mixed in chloroform 0.