The thermodynamic basis for the binding of lipids to annexin a5

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The thermodynamic basis for the binding of lipids to annexin a5

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Knutson, Kristofer James

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2009-12

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Abstract

Protein-membrane interactions are a vital mechanism of propagating signals both across the membrane and between cells. To control the magnitude and specificity of this type of cell signaling at the membrane, clustering of similar lipids and proteins has been observed in the cell via the formation of lipid microdomains. To address the thermodynamic basis of lipid induced signal propagation, we investigated how lipid microdomains form in response to annexin a5 binding to model membranes using Isothermal Titration Calorimetry (ITC). Annexins are known to bind to negatively charged (e.g., phosphatidylserine [PS]) membranes in a Ca2+-dependent manner. Based on Differential Scanning Calorimetry (DSC) results, we suggest that annexin functions to order lipid acyl chains upon binding and that the ordering of phospholipids can lead to the formation of microdomains. Using ITC, we have analyzed the membrane binding affinity of annexin for both gel and fluid state mixtures. Binding analysis of these isotherms shows that annexin binds fluid state mixtures with a significantly lower Kd than gel state (acyl chain ordered) lipids, which would be consistent with the hypothesis that binding of annexin a5 orders the acyl chains of the phospholipids. In addition, because the binding is entropically dominated but exhibits greater affinity for fluid compared to gel state lipids, we suggest that annexin binding is driven by the release of water molecules and ions as fluid lipids have more waters of hydration. Interestingly, the enthalpy associated with the binding process for both gel and fluid state lipid mixtures is small, indicative of a weak enthalpic association and suggestive of entropically mediated binding. We also present the binding of Eu3+ by a lanthanide binding complex (Tetra(N-(tert-butyl)-acetamide)-1,13-diamino-3,6,9-trioxadecane).

Keywords

Protein-membrane

Thermodynamics

Membrane

Lipids

Chemistry

Cell

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University of Minesota M.S. thesis. December 2009. Major: Chemistry. Advisor: Prof. Anne Hinderliter. 1 computer file (PDF); vii, 41 pages.

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Knutson, Kristofer James. (2009). The thermodynamic basis for the binding of lipids to annexin a5. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/59906.

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