Small-angle X-ray Scattering of Apolipoprotein A-IV Reveals the Importance of Its Termini for Structural Stability

Deng, Xiaolong; Morris, Jamie; Chaton, Catherine T.; Schröder, Gunnar F.; Davidson, W. Sean; Thompson, Thomas B.

doi:10.1074/jbc.m112.436709

Cited by 12 publications

(19 citation statements)

References 39 publications

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“…Although the functional K ATP and calcium channels are required for the action of apoA-IV on insulin secretion, apoA-IV did not act directly to stimulate calcium infl ux. Instead, the action of apoA-IV is downstream of Ca 2+ infl ux and amplifi es insulin exocytosis ( 20 ). While these data suggest that apoA-IV acts on the later stages of insulin secretion, the precise molecular mechanism remains to be elucidated.…”

Section: Summary and Prospectusmentioning

confidence: 80%

“…Analysis of point mutations and deletions revealed that the lipid binding properties are conferred primarily by the central helices. Regions near the N and C termini, on the other hand, raise the activation energy for lipid binding, apparently through direct interaction of the two ends that stabilizes the lipid-free form ( 20 ). Crystallography data revealed that lipid-free apoA-IV exists primarily as a homodimer with the two molecules aligned in anti-parallel fashion.…”

Section: Apoa-iv Gene Protein Structure and Genetic Variantsmentioning

confidence: 99%

“…Similar to the related protein apoA-I, apoA-IV consists of 12 amphipathic helices that facilitate both lipid binding and aqueous interaction, resulting in a protein that binds to the surface of lipid particles but is readily exchangeable, consistent with its role in metabolism of both chylomicrons and HDL, as well as its abundance lipid-free in the circulation. Key features of the structure and function of these helices and other aspects of apoA-IV were determined by crystallography, cross-linking, and mutational analyses of lipid binding properties ( 19,20 ). Analysis of point mutations and deletions revealed that the lipid binding properties are conferred primarily by the central helices.…”

Section: Apoa-iv Gene Protein Structure and Genetic Variantsmentioning

confidence: 99%

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Apolipoprotein A-IV: a protein intimately involved in metabolism

Wang

Kohan

et al. 2015

Journal of Lipid Research

127

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Section: Summary and Prospectusmentioning

confidence: 80%

Section: Apoa-iv Gene Protein Structure and Genetic Variantsmentioning

confidence: 99%

Section: Apoa-iv Gene Protein Structure and Genetic Variantsmentioning

confidence: 99%

See 1 more Smart Citation

Apolipoprotein A-IV: a protein intimately involved in metabolism

Wang

Kohan

et al. 2015

Journal of Lipid Research

127

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“…Previously, we established that apoA-IV is highly stable for days in its dimeric and monomeric forms when incubated below 25°C (37). However, at 37°C, isolated dimers redistribute to a 30:70 dimer:monomer mixture within 24 h (Fig.…”

Section: B and C)mentioning

confidence: 99%

“…However, at 37°C, isolated dimers redistribute to a 30:70 dimer:monomer mixture within 24 h (Fig. 3, A and E) (37). To assess the stability of the mutants, we FIGURE 3.…”

Section: B and C)mentioning

confidence: 99%

Role of Conserved Proline Residues in Human Apolipoprotein A-IV Structure and Function

Deng

Walker

Morris

et al. 2015

Journal of Biological Chemistry

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Background: New structures of apolipoprotein (apo)A-IV reveal aligned, conserved proline residues of unknown function. Results: Increasing deletion of prolines stabilizes apoA-IV and increases self-association but also increases lipid affinity and cholesterol efflux. Conclusion: Proline residues play a concerted role in destabilizing the apoA-IV structure and modulate its function. Significance: This is the first detailed study of the structural role of proline and of a stable trimeric exchangeable apolipoprotein.

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Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

Bhale,

Meilhac,

d'Hellencourt

et al. 2024

BioFactors

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High‐density lipoproteins (HDLs) play a vital role in lipid metabolism and cardiovascular health, as they are intricately involved in cholesterol transport and inflammation modulation. The proteome of HDL particles is indeed complex and distinct from other components in the bloodstream. Proteomics studies have identified nearly 285 different proteins associated with HDL; however, this review focuses more on the 15 or so traditionally named “apo” lipoproteins. Important lipid metabolizing enzymes closely working with the apolipoproteins are also discussed. Apolipoproteins stand out for their integral role in HDL stability, structure, function, and metabolism. The unique structure and functions of each apolipoprotein influence important processes such as inflammation regulation and lipid metabolism. These interactions also shape the stability and performance of HDL particles. HDLs apolipoproteins have multifaceted roles beyond cardiovascular diseases (CVDs) and are involved in various physiological processes and disease states. Therefore, a detailed exploration of these apolipoproteins can offer valuable insights into potential diagnostic markers and therapeutic targets. This comprehensive review article aims to provide an in‐depth understanding of HDL apolipoproteins, highlighting their distinct structures, functions, and contributions to various physiological processes. Exploiting this knowledge holds great potential for improving HDL function, enhancing cholesterol efflux, and modulating inflammatory processes, ultimately benefiting individuals by limiting the risks associated with CVDs and other inflammation‐based pathologies. Understanding the nature of all 15 apolipoproteins expands our knowledge of HDL metabolism, sheds light on their pathological implications, and paves the way for advancements in the diagnosis, prevention, and treatment of lipid and inflammatory‐related disorders.

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Small-angle X-ray Scattering of Apolipoprotein A-IV Reveals the Importance of Its Termini for Structural Stability

Cited by 12 publications

References 39 publications

Apolipoprotein A-IV: a protein intimately involved in metabolism

Apolipoprotein A-IV: a protein intimately involved in metabolism

Role of Conserved Proline Residues in Human Apolipoprotein A-IV Structure and Function

Cholesterol transport and beyond: Illuminating the versatile functions of HDL apolipoproteins through structural insights and functional implications

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