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Start Over Descriptor "structure–function analyses" Publisher elife sciences publications, ltd
2 results on '"structure–function analyses"'

1. Structural basis of phosphatidylcholine recognition by the C2–domain of cytosolic phospholipase A2α

Author

Yong-Guang Gao, Ngoc T. Vu, Daniel J. Stephenson, Rhoderick E. Brown, Charles E. Chalfant, Lucy Malinina, Yoshinori Hirano, Dinshaw J. Patel, and Dhirendra K. Simanshu

Subjects
C2-domain of cytoplasmic phospholipase A2 alpha, QH301-705.5, Cations, Divalent, Science, Structural Biology and Molecular Biophysics, DNA Mutational Analysis, Plasma protein binding, Phospholipase, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0302 clinical medicine, Phosphatidylcholine, structure-function analyses, Phosphatidylinositol, Biology (General), structural mapping of phosphatidylcholine binding site, Binding selectivity, 030304 developmental biology, C2 domain, 0303 health sciences, General Immunology and Microbiology, General Neuroscience, Group IV Phospholipases A2, Correction, General Medicine, Phosphatidylserine, Golgi apparatus, Chicken, Recombinant Proteins, chemistry, Amino Acid Substitution, symbols, Biophysics, Mutagenesis, Site-Directed, Phosphatidylcholines, Medicine, Calcium, 030217 neurology & neurosurgery, Protein Binding, Research Article, Human
Abstract

Ca2+-stimulated translocation of cytosolic phospholipase A2α (cPLA2α) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLA2α preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report the structure of the cPLA2α C2-domain (at 2.2 Å resolution), which contains bound 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) and Ca2+ ions. Two Ca2+ are complexed at previously reported locations in the lipid-free C2-domain. One of these Ca2+ions, along with a third Ca2+, bridges the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid headgroup recognition via cation–π interaction with the PC trimethylammonium group. Mutagenesis analyses confirm that Tyr96 and Asn65 function in PC binding selectivity by the C2-domain and in the regulation of cPLA2α activity. The DHPC-binding mode of the cPLA2α C2-domain, which differs from phosphatidylserine or phosphatidylinositol 4,5-bisphosphate binding by other C2-domains, expands and deepens knowledge of the lipid-binding mechanisms mediated by C2-domains.

Published
2019

2. Structural basis of phosphatidylcholine recognition by the C2-domain of cytosolic phospholipase A 2 α.

Author

Hirano Y, Gao YG, Stephenson DJ, Vu NT, Malinina L, Simanshu DK, Chalfant CE, Patel DJ, and Brown RE

Subjects
Amino Acid Substitution, Cations, Divalent metabolism, DNA Mutational Analysis, Group IV Phospholipases A2 genetics, Mutagenesis, Site-Directed, Protein Binding, Recombinant Proteins chemistry, Recombinant Proteins metabolism, Calcium metabolism, Group IV Phospholipases A2 chemistry, Group IV Phospholipases A2 metabolism, Phosphatidylcholines metabolism
Abstract

Ca 2+ -stimulated translocation of cytosolic phospholipase A 2 α (cPLA 2 α) to the Golgi induces arachidonic acid production, the rate-limiting step in pro-inflammatory eicosanoid synthesis. Structural insights into the cPLA 2 α preference for phosphatidylcholine (PC)-enriched membranes have remained elusive. Here, we report the structure of the cPLA 2 α C2-domain (at 2.2 Å resolution), which contains bound 1,2-dihexanoyl- sn -glycero-3-phosphocholine (DHPC) and Ca 2+ ions. Two Ca 2+ are complexed at previously reported locations in the lipid-free C2-domain. One of these Ca 2+ ions, along with a third Ca 2+ , bridges the C2-domain to the DHPC phosphate group, which also interacts with Asn65. Tyr96 plays a key role in lipid headgroup recognition via cation-π interaction with the PC trimethylammonium group. Mutagenesis analyses confirm that Tyr96 and Asn65 function in PC binding selectivity by the C2-domain and in the regulation of cPLA 2 α activity. The DHPC-binding mode of the cPLA 2 α C2-domain, which differs from phosphatidylserine or phosphatidylinositol 4,5-bisphosphate binding by other C2-domains, expands and deepens knowledge of the lipid-binding mechanisms mediated by C2-domains., Competing Interests: YH, YG, DS, NV, LM, DS, CC, DP, RB No competing interests declared, (© 2019, Hirano et al.)

Published
2019
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