Conformational and Disorder to Order Transitions in Proteins: Structure / Function Correlation in Apolipoproteins

Campos‐Terán, José; Espinosa, Paola Mendoza; Mas, Jaime; Castillo, Rolando

doi:10.5772/37217

Cited by 1 publication

(2 citation statements)

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“…Finally, we observed a size uniformity of the steric zipper and adjacent regions, a property related to protein–protein interactions that drive amyloid-like formation. The existence of unstructured segments at the N- and C-terminal domains of apoA-I makes the protein susceptible to enzymatic hydrolysis [ 36 ], phenomenon that increases the probability for the generation of highly hydrophobic autoimmune structures that in turn might induce an inflammatory response [ 33 , 37 , 38 ] promoting the generation of nucleation centers important in the formation of amyloid-like fibrils (Fig. 5 ) [ 39 – 42 ].…”

Section: Discussionmentioning

confidence: 99%

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Microenvironmentally controlled secondary structure motifs of apolipoprotein A-I derived peptides

et al. 2014

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The structure of apolipoprotein A-I (apoA-I), the major protein of HDL, has been extensively studied in past years. Nevertheless, its corresponding three-dimensional structure has been difficult to obtain due to the frequent conformational changes observed depending on the microenvironment. Although the function of each helical segment of this protein remains unclear, it has been observed that the apoA-I amino (N) and carboxy-end (C) domains are directly involved in receptor-recognition, processes that determine the diameter for HDL particles. In addition, it has been observed that the high structural plasticity of these segments might be related to several amyloidogenic processes. In this work, we studied a series of peptides derived from the N- and C-terminal domains representing the most hydrophobic segments of apoA-I. Measurements carried out using circular dichroism in all tested peptides evidenced that the lipid environment promotes the formation of α-helical structures, whereas an aqueous environment facilitates a strong tendency to adopt β-sheet/disordered conformations. Electron microscopy observations showed the formation of amyloid-like structures similar to those found in other well-defined amyloidogenic proteins. Interestingly, when the apoA-I peptides were incubated under conditions that promote stable globular structures, two of the peptides studied were cytotoxic to microglia and mouse macrophage cells. Our findings provide an insight into the physicochemical properties of key segments contained in apoA-I which may be implicated in disorder-to-order transitions that in turn maintain the delicate equilibrium between both, native and abnormal conformations, and therefore control its propensity to become involved in pathological processes.

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Section: Discussionmentioning

confidence: 99%

“…Peptides released by proteolysis might form amyloidogenic structures that can be organized first as micelle-like peptides that can evolve to form globular or protofibrillar structures depending on their residue composition [ 42 , 47 ]. Modified from [ 33 ] …”

Section: Discussionmentioning

confidence: 99%