Annexin A4 binding to anionic phospholipid vesicles modulated by pH and calcium
Olaf Zschörnig1, Frank Opitz, Matthias Müller
1Institute of Medical Physics and Biophysics, University of Leipzig, Leipzig, Germany. olaf.zschoernig@medizin.uni-leipzig.de
European Biophysics Journal : EBJ
|April 19, 2007
Summary
Annexin A4 binds strongly to acidic phospholipids at acidic pH, but requires calcium at neutral pH. This protein influences vesicle fusion and leakage, with its conformation and binding behavior varying with pH.
Area of Science:
- Biochemistry
- Molecular Biology
- Membrane Biophysics
Background:
- Annexin A4 is a Ca(2+)-binding protein implicated in exocytosis and coagulation.
- Annexin functions are linked to their ability to bind acidic phospholipids.
Purpose of the Study:
- Investigate the interaction of Annexin A4 with phosphatidylserine (PS) and phosphatidic acid (PA) large unilamellar vesicles (LUVs).
- Determine the influence of pH and Ca(2+) on Annexin A4 binding, vesicle fusion, and leakage.
Main Methods:
- Utilized large unilamellar vesicles (LUVs) composed of PS or PA.
- Studied Annexin A4 binding at neutral (pH 7.4) and acidic (pH 4) conditions.
- Assessed the effects of Ca(2+) on binding, vesicle fusion, and Ca(2+)-independent leakage.
Main Results:
- Annexin A4 strongly binds PS/PA LUVs at acidic pH, but requires Ca(2+) for strong binding at neutral pH.
- Binding at acidic pH induces greater vesicle dehydration and fusion compared to neutral pH.
- Annexin A4 facilitates Ca(2+)-independent leakage of PS/PA LUVs, enhanced at acidic pH.
Conclusions:
- Annexin A4 conformation and membrane interaction differ significantly between acidic and neutral pH.
- At acidic pH, Annexin A4 may penetrate the lipid bilayer, while at neutral pH, it localizes to the vesicle surface.
- Annexin A4's binding stoichiometry to vesicles varies, potentially due to its Ca(2+) binding sites.
More Related Videos
06:32A Thermoplasmonic Approach for Investigating Plasma Membrane Repair in Living Cells and Model Membranes
Published on: January 19, 2024
10:31A Liposome Membrane Permeability Assay for Investigating the Effects of Phosphatidylinositol Phosphate Groups on Membranotropic Action of Venom PLA2
Published on: September 26, 2025
Related Concept Videos
01:42Phosphoinositides and PIPs
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
01:11IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:26Fusion of Secretory Vesicles with the Plasma Membrane
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
01:32Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
01:17Intracellular Signaling Affects Focal Adhesions
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...