FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2082439972> ?p ?o ?g. }

• W2082439972 endingPage "1953" @default.
• W2082439972 startingPage "1934" @default.
• W2082439972 abstract "Phospholipases C (PLCs) reversibly associate with membranes to hydrolyze phosphatidylinositol-4, 5-bisphosphate (PI[4,5]P2) and comprise four main classes: β, γ, δ, and ε. Most eukaryotic PLCs contain a single, N-terminal pleckstrin homology (PH) domain, which is thought to play an important role in membrane targeting. The structure of a single PLC PH domain, that from PLCδ1, has been determined; this PH domain binds PI(4,5)P2 with high affinity and stereospecificity and has served as a paradigm for PH domain functionality. However, experimental studies demonstrate that PH domains from different PLC classes exhibit diverse modes of membrane interaction, reflecting the dissimilarity in their amino acid sequences. To elucidate the structural basis for their differential membrane-binding specificities, we modeled the three-dimensional structures of all mammalian PLC PH domains by using bioinformatic tools and calculated their biophysical properties by using continuum electrostatic approaches. Our computational analysis accounts for a large body of experimental data, provides predictions for those PH domains with unknown functions, and indicates functional roles for regions other than the canonical lipid-binding site identified in the PLCδ1-PH structure. In particular, our calculations predict that (1) members from each of the four PLC classes exhibit strikingly different electrostatic profiles than those ordinarily observed for PH domains in general, (2) nonspecific electrostatic interactions contribute to the membrane localization of PLCδ-, PLCγ-, and PLCβ-PH domains, and (3) phosphorylation regulates the interaction of PLCβ-PH with its effectors through electrostatic repulsion. Our molecular models for PH domains from all of the PLC classes clearly demonstrate how a common structural fold can serve as a scaffold for a wide range of surface features and biophysical properties that support distinctive functional roles." @default.
• W2082439972 created "2016-06-24" @default.
• W2082439972 creator A5081710529 @default.
• W2082439972 creator A5082996631 @default.
• W2082439972 date "2003-09-01" @default.
• W2082439972 modified "2023-10-16" @default.
• W2082439972 title "Molecular modeling of the membrane targeting of phospholipase C pleckstrin homology domains" @default.
• W2082439972 cites W1234417371 @default.
• W2082439972 cites W1486102976 @default.
• W2082439972 cites W1499450468 @default.
• W2082439972 cites W1518153787 @default.
• W2082439972 cites W1524556134 @default.
• W2082439972 cites W1558700872 @default.
• W2082439972 cites W1582659466 @default.
• W2082439972 cites W1602800967 @default.
• W2082439972 cites W1617760412 @default.
• W2082439972 cites W1884928912 @default.
• W2082439972 cites W1895415431 @default.
• W2082439972 cites W1958742527 @default.
• W2082439972 cites W1964011658 @default.
• W2082439972 cites W1964442771 @default.
• W2082439972 cites W1970692622 @default.
• W2082439972 cites W1971113488 @default.
• W2082439972 cites W1977170693 @default.
• W2082439972 cites W1977922844 @default.
• W2082439972 cites W1979817897 @default.
• W2082439972 cites W1981182586 @default.
• W2082439972 cites W1985435142 @default.
• W2082439972 cites W1987215061 @default.
• W2082439972 cites W1994063020 @default.
• W2082439972 cites W1995846848 @default.
• W2082439972 cites W1997784032 @default.
• W2082439972 cites W1998712463 @default.
• W2082439972 cites W1999493392 @default.
• W2082439972 cites W2000774142 @default.
• W2082439972 cites W2001557131 @default.
• W2082439972 cites W2002659345 @default.
• W2082439972 cites W2003997759 @default.
• W2082439972 cites W2004228538 @default.
• W2082439972 cites W2004357717 @default.
• W2082439972 cites W2006455216 @default.
• W2082439972 cites W2008726339 @default.
• W2082439972 cites W2011214599 @default.
• W2082439972 cites W2011313782 @default.
• W2082439972 cites W2012992067 @default.
• W2082439972 cites W2014065789 @default.
• W2082439972 cites W2016441216 @default.
• W2082439972 cites W2018001030 @default.
• W2082439972 cites W2021534482 @default.
• W2082439972 cites W2021717885 @default.
• W2082439972 cites W2022964566 @default.
• W2082439972 cites W2026593599 @default.
• W2082439972 cites W2027557494 @default.
• W2082439972 cites W2028125482 @default.
• W2082439972 cites W2028843689 @default.
• W2082439972 cites W2031815624 @default.
• W2082439972 cites W2032518125 @default.
• W2082439972 cites W2037303082 @default.
• W2082439972 cites W2038126024 @default.
• W2082439972 cites W2041305500 @default.
• W2082439972 cites W2042866020 @default.
• W2082439972 cites W2047163848 @default.
• W2082439972 cites W2048622566 @default.
• W2082439972 cites W2051889119 @default.
• W2082439972 cites W2055043387 @default.
• W2082439972 cites W2065283382 @default.
• W2082439972 cites W2065928074 @default.
• W2082439972 cites W2066094617 @default.
• W2082439972 cites W2067173516 @default.
• W2082439972 cites W2068488447 @default.
• W2082439972 cites W2069109360 @default.
• W2082439972 cites W2071486470 @default.
• W2082439972 cites W2072459093 @default.
• W2082439972 cites W2075095368 @default.
• W2082439972 cites W2079173223 @default.
• W2082439972 cites W2079685674 @default.
• W2082439972 cites W2080264403 @default.
• W2082439972 cites W2082688327 @default.
• W2082439972 cites W2084466582 @default.
• W2082439972 cites W2087064593 @default.
• W2082439972 cites W2089663411 @default.
• W2082439972 cites W2090429239 @default.
• W2082439972 cites W2092249847 @default.
• W2082439972 cites W2092275582 @default.
• W2082439972 cites W2093253631 @default.
• W2082439972 cites W2094841666 @default.
• W2082439972 cites W2096549360 @default.
• W2082439972 cites W2102436071 @default.
• W2082439972 cites W2106154817 @default.
• W2082439972 cites W2106315897 @default.
• W2082439972 cites W2106882534 @default.
• W2082439972 cites W2107566660 @default.
• W2082439972 cites W2112012991 @default.
• W2082439972 cites W2112305018 @default.
• W2082439972 cites W2114049512 @default.
• W2082439972 cites W2117111749 @default.
• W2082439972 cites W2119806797 @default.
• W2082439972 cites W2121560377 @default.

• next