The Lipid Binding Activity of the Exchangeable Apolipoprotein Apolipophorin-III Correlates with the Formation of a Partially Folded Conformation†

Biochemistry ◽  
1998 ◽  
Vol 37 (28) ◽  
pp. 10203-10210 ◽  
Author(s):  
Jose L. Soulages ◽  
Omid J. Bendavid
Keyword(s):  
Lipid Binding ◽  
Binding Activity ◽  
Apolipophorin Iii ◽  
Exchangeable Apolipoprotein ◽  
Partially Folded Conformation

Abstract 391: Apolipoprotein E3, Apolipoprotein AI, and Apolipophorin III Chimeras Provide Insight Into the Domain Organization of Apolipoproteins

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
James V Horn ◽  
Mark Lek ◽  
Nnejiuwa Ibe ◽  
Rachel A Ellena ◽  
Wendy H Beck ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Dominant Role ◽  
Lipoprotein Metabolism ◽  
Lipid Binding ◽  
Binding Activity ◽  
Domain Model ◽  
Helix Bundle ◽  
Apolipophorin Iii ◽  
Helical Content ◽  
The Stability

Apolipoproteins (apo) A-I and E are exchangeable apolipoproteins that play a dominant role in regulating lipoprotein metabolism. They are composed of a series of amphipathic α-helices, which are organized into an N-terminal (NT) helix bundle domain and a smaller C-terminal (CT) domain. The objective of the current study is to understand the functional and structural role of the domains of these proteins by “domain swapping” using apoE3 and apoAI, both of which bear a 4-helix bundle in their NT domain, and apolipophorin III (apoLp-III), a monomeric one-domain model apolipoprotein. A series of chimeric apolipoproteins were generate: apoE3-NT/apoAI-CT, apoAI-NT/apoE-CT and apoLp-III/apoA-I-CT. The α-helical content of the chimeras was comparable to that of the parent proteins. Unfolding studies indicated that addition of CT-apoE3 to NT-apoAI conferred more stability to apoAI. While addition of CT-apoAI to NT-apoE3 had no significant effect on the stability of apoE3, addition of NT-apoAI to apoLp-III increased the stability of apoLp-III. Moreover, apoLp-III switched from a monomeric to an oligomeric protein upon addition of CT-apoAI, showing that CT-apoAI has a strong tendency to self-associate. Addition of CT-apoAI to NT-apoE or apoLp-III increased the lipid binding activity by ~ 10-fold, while addition of apoE-CT to apoA-I-NT had no measurable effect on the lipid binding activity. All three chimeras promote ABCA1-mediated cholesterol efflux from J774 macrophages, with the efflux capability being highest for apoAI-NT/apoE-CT. Whereas apoE3-NT/apoAI-CT elicits LDLr binding ability, apoAI-NT/apoE-CT did not. These results suggest that CT of apoAI is a strong promoter of lipid binding, while CT of apoE3 can improve cholesterol efflux ability of apoAI.

scholarly journals Essential Role of the Conformational Flexibility of Helices 1 and 5 on the Lipid Binding Activity of Apolipophorin-III

2001 ◽  
Vol 276 (36) ◽  
pp. 34162-34166 ◽  
Author(s):  
Jose L. Soulages ◽  
Estela L. Arrese ◽  
Palaniappan S. Chetty ◽  
Veronica Rodriguez
Keyword(s):  
Essential Role ◽  
Conformational Flexibility ◽  
Lipid Binding ◽  
Binding Activity ◽  
Apolipophorin Iii

scholarly journals Lipid-Binding Activity of Intrinsically Unstructured Cytoplasmic Domains of Multichain Immune Recognition Receptor Signaling Subunits†

Biochemistry ◽  
2006 ◽  
Vol 45 (51) ◽  
pp. 15731-15739 ◽  
Author(s):  
Alexander B. Sigalov ◽  
Dikran A. Aivazian ◽  
Vladimir N. Uversky ◽  
Lawrence J. Stern
Keyword(s):  
Lipid Binding ◽  
Binding Activity ◽  
Immune Recognition ◽  
Receptor Signaling ◽  
Cytoplasmic Domains ◽  
Recognition Receptor

scholarly journals Replacement of helix 1' enhances the lipid binding activity of apoE3 N-terminal domain

FEBS Journal ◽  
2006 ◽  
Vol 273 (3) ◽  
pp. 558-567 ◽  
Author(s):  
Katherine A. Redmond ◽  
Conrad Murphy ◽  
Vasanthy Narayanaswami ◽  
Robert S. Kiss ◽  
Paul Hauser ◽  
...  
Keyword(s):  
Lipid Binding ◽  
Binding Activity ◽  
Terminal Domain
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