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Heme binding inhibits the fibrillization of amyloidogenic apomyoglobin and determines lack of aggregate cytotoxicity
Author(s) -
Iannuzzi Clara,
Vilasi Silvia,
Portaccio Marianna,
Irace Gaetano,
Sirangelo Ivana
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062471107
Subject(s) - chemistry , myoglobin , protein aggregation , amyloid (mycology) , heme , biophysics , circular dichroism , fibril , protein folding , globular protein , protein structure , thioflavin , biochemistry , enzyme , inorganic chemistry , biology , medicine , disease , pathology , alzheimer's disease
Myoglobin is an α‐helical globular protein containing two highly conserved tryptophanyl residues at positions 7 and 14 in the N‐terminal region. The double W/F replacement renders apomyoglobin highly susceptible to aggregation and amyloid‐like fibril formation under physiological conditions. In this work we analyze the early stage of W7FW14F apomyoglobin aggregation following the time dependence of the process by far‐UV CD, Fourier‐transform infrared (FTIR) spectroscopy, and heme‐binding properties. The results show that the aggregation of W7FW14F apomyoglobin starts from a native‐like globin state able to bind the prosthetic group with spectroscopic properties similar to those observed for wild‐type apoprotein. Nevertheless, it rapidly aggregates, forming amyloid fibrils. However, when the prosthetic group is added before the beginning of aggregation, amyloid fibrillization is inhibited, although the aggregation process is not prevented. Moreover, the apomyoglobin aggregates formed in these conditions are not cytotoxic differently from what is observed for all amyloidogenic proteins. These results open new insights into the relationship between the structure adopted by the protein into the aggregates and their ability to trigger the impairment of cell viability.

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