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dc.contributor.authorYadav, Rahul
dc.contributor.authorVattepu, Ravi
dc.contributor.authorBeck, Moriah R.
dc.date.accessioned2016-11-17T23:10:55Z
dc.date.available2016-11-17T23:10:55Z
dc.date.issued2016-10-09
dc.identifier.citationYadav, Rahul; Vattepu, Ravi; Beck, Moriah R. 2016. Phosphoinositide binding inhibits actin crosslinking and polymerization by palladin. Journal of Molecular Biology, vol. 428:no. 20, 9 October 2016:pp 4031–4047en_US
dc.identifier.issn0022-2836
dc.identifier.otherWOS:000385324000012
dc.identifier.urihttp://dx.doi.org/10.1016/j.jmb.2016.07.018
dc.identifier.urihttp://hdl.handle.net/10057/12683
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractActin cytoskeleton remodeling requires the coordinated action of a large number of actin binding proteins that reorganize the actin cytoskeleton by promoting polymerization, stabilizing filaments, causing branching, or crosslinking filaments. Palladin is a key cytoskeletal actin binding protein whose normal function is to enable cell motility during development of tissues and organs of the embryo and in wound healing, but palladin is also responsible for regulating the ability of cancer cells to become invasive and metastatic. The membrane phosphoinositide phosphatidylinositol (PI) 4,5-bisphosphate [PI(4,5)P-2] is a well-known precursor for intracellular signaling and a bona fide regulator of actin cytoskeleton reorganization. Our results show that two palladin domains [immunoglobulin (Ig) 3 and 34] interact with the head group of PI(4,5)P-2 with moderate affinity (apparent K-d = 17 mu M). Interactions with PI(4,5)P-2 decrease the actin polymerizing activity of Ig domain 3 of palladin (Palld-Ig3). Furthermore, NMR titration and docking studies show that residues K38 and K51, which are present on the beta-sheet C and D, form salt bridges with the head group of PI(4,5)P-2. Moreover, charge neutralization at lysine 38 in the Palld-Ig3 domain severely limits the actin polymerizing and bundling activity of Palld-Ig3. Our results provide biochemical proof that PI(4,5)P-2 functions as a moderator of palladin activity and have also identified residues directly involved in the crosslinking activity of palladin.en_US
dc.description.sponsorshipThe project was supported by a new investigator grant to M.R.B. from the Centers for Biomedical Research Excellence (COBRE) grant from the NCCR (5P20RR017708) and the NIGMS (8P20GM103420) and by an Institutional Development Award (IDeA) from the NIGMS of the NIH under grant number P20 GM103418.en_US
dc.language.isoen_USen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofseriesJournal of Molecular Biology;v.428:no.20
dc.subjectPhospholipiden_US
dc.subjectActin cytoskeletonen_US
dc.subjectRegulationen_US
dc.subjectElectrostaticsen_US
dc.subjectNMRen_US
dc.titlePhosphoinositide binding inhibits actin crosslinking and polymerization by palladinen_US
dc.typeArticleen_US
dc.rights.holder(C) 2016 Elsevier Ltd. All rights reserved.en_US


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