NDLI: Lateral Sequestration of Phosphatidylinositol 4,5-Bisphosphate by the Basic Effector Domain of Myristoylated Alanine-rich C Kinase Substrate Is Due to Nonspecific Electrostatic Interactions

Content Provider	Journal of Biological Chemistry (JBC)
Author	Wang, Jiyao Gambhir, Alok Hangyás-Mihályné, Gyöngyi Murray, Diana Golebiewska, Urszula McLaughlin, Stuart
Description	A peptide lacking 3 Lys residues at the C terminus and 5 Lys residues at the N-terminus of MARCKS-(151–175) (ΔNΔC-MARCKS)
Abstract	A peptide corresponding to the basic (+13), unstructured effector domain of myristoylated alanine-rich C kinase substrate (MARCKS) binds strongly to membranes containing phosphatidylinositol 4,5-bisphosphate (PIP2). Although aromatic residues contribute to the binding, three experiments suggest the binding is driven mainly by nonspecific local electrostatic interactions. First, peptides with 13 basic residues, Lys-13 and Arg-13, bind to PIP2-containing vesicles with the same high affinity as the effector domain peptide. Second, removing basic residues from the effector domain peptide reduces the binding energy by an amount that correlates with the number of charges removed. Third, peptides corresponding to a basic region in GAP43 and MARCKS effector domain-like regions in other proteins (e.g. MacMARCKS, adducin, Drosophila A kinase anchor protein 200, and N-methyl-d-aspartate receptor) also bind with an energy that correlates with the number of basic residues. Kinetic measurements suggest the effector domain binds to several PIP2. Theoretical calculations show the effector domain produces a local positive potential, even when bound to a bilayer with 33% monovalent acidic lipids, and should thus sequester PIP2 laterally. This electrostatic sequestration was observed experimentally using a phospholipase C assay. Our results are consistent with the hypothesis that MARCKS could reversibly sequester much of the PIP2 in the plasma membrane.
Related Links	http://www.jbc.org/content/277/37/34401.abstract
Ending Page	34412
Starting Page	34401
Page Count	12
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	37
Volume Number	277
DOI	10.1074/jbc.M203954200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2002-09-13
Access Restriction	Open
Subject Keyword	5)P2, phosphatidylinositol 4,5-bisphosphate (PIP2 or PI(4) 4)P2, phosphatidylinositol 3,4-bisphosphate (PI(3) Inositol 1,4,5-trisphosphate (IP3) Phosphatidylcholine (PC) Phosphatidylserine (PS) Myristoylated alanine-rich C kinase substrate (MARCKS) A peptide corresponding to residues 151−175 of bovine MARCKS (MARCKS-(151−175)) A peptide lacking 3 Lys residues at the C terminus of MARCKS-(151–175) (ΔC-MARCKS) A peptide lacking 5 Lys residues at the N terminus of MARCKS-(151–175) (ΔN-MARCKS) A peptide with all 5 Phe replaced by Ala in MARCKS-(151–175) (FA-MARCKS) Macrophage-enriched myristoylated alanine-rich C kinase substrate (MacMARCKS) Drosophila A kinase anchor protein 200 (DAKAP200) N-methyl-d-aspartate receptor (NMDA receptor) Growth-associated protein of Mr 43,000 (GAP43) Cortical cytoskeleton-associated protein of approximate molecular mass 23 kDa (CAP23) Neuronal Wiskott-Aldrich Syndrome protein (N-WASP) Secretory carrier membrane protein 2 (SCAMP2) A-kinase anchoring protein 79 (AKAP79) Phosphatidylcholine-specific phospholipase D (PLD) Phosphoinositide-specific phospholipase C (PLC) Pleckstrin homology (PH) PH domain of PLC-δ1 (PLC-PH) Protein kinase C (PKC) N-ethylmaleimide (NEM) Large unilamellar vesicle (LUV) Multilamellar vesicle (MLV) Nonlinear Poisson-Boltzmann (NLPB) Matrix-assisted laser desorption ionization (MALDI) N,N-dimethylformamide (DMF) 4-morpholinepropanesulfonic acid (MOPS) MECHANISMS OF SIGNAL TRANSDUCTION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

The Effector Domain of Myristoylated Alanine-rich C Kinase Substrate Binds Strongly to Phosphatidylinositol 4,5-Bisphosphate

Myristoylated Alanine-rich C Kinase Substrate (MARCKS) Sequesters Spin-labeled Phosphatidylinositol 4,5-Bisphosphate in Lipid Bilayers

Myristoylated Alanine-rich C Kinase Substrate (MARCKS) Produces Reversible Inhibition of Phospholipase C by Sequestering Phosphatidylinositol 4,5-Bisphosphate in Lateral Domains

A peptide that inhibits function of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) reduces lung cancer metastasis

Protein kinase C-mediated phosphorylation and calmodulin binding of recombinant myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein.

Myristoylated alanine-rich C kinase substrate coordinates native TRPC1 channel activation by phosphatidylinositol 4,5-bisphosphate and protein kinase C in vascular smooth muscle

A possible role of myristoylated alanine-rich C kinase substrate in endocytic pathway of Alzheimer’s disease

Myristoylated alanine-rich C kinase substrate (MARCKS): a multirole signaling protein in cancers

Interaction of myristoylated alanine-rich protein kinase C substrate (MARCKS) with membrane phospholipids.

Lateral Sequestration of Phosphatidylinositol 4,5-Bisphosphate by the Basic Effector Domain of Myristoylated Alanine-rich C Kinase Substrate Is Due to Nonspecific Electrostatic Interactions

Similar Documents

The Effector Domain of Myristoylated Alanine-rich C Kinase Substrate Binds Strongly to Phosphatidylinositol 4,5-Bisphosphate

Myristoylated Alanine-rich C Kinase Substrate (MARCKS) Sequesters Spin-labeled Phosphatidylinositol 4,5-Bisphosphate in Lipid Bilayers

Myristoylated Alanine-rich C Kinase Substrate (MARCKS) Produces Reversible Inhibition of Phospholipase C by Sequestering Phosphatidylinositol 4,5-Bisphosphate in Lateral Domains

A peptide that inhibits function of Myristoylated Alanine-Rich C Kinase Substrate (MARCKS) reduces lung cancer metastasis

Protein kinase C-mediated phosphorylation and calmodulin binding of recombinant myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein.

Myristoylated alanine-rich C kinase substrate coordinates native TRPC1 channel activation by phosphatidylinositol 4,5-bisphosphate and protein kinase C in vascular smooth muscle

A possible role of myristoylated alanine-rich C kinase substrate in endocytic pathway of Alzheimer’s disease

Myristoylated alanine-rich C kinase substrate (MARCKS): a multirole signaling protein in cancers

Interaction of myristoylated alanine-rich protein kinase C substrate (MARCKS) with membrane phospholipids.

Lateral Sequestration of Phosphatidylinositol 4,5-Bisphosphate by the Basic Effector Domain of Myristoylated Alanine-rich C Kinase Substrate Is Due to Nonspecific Electrostatic Interactions