title: The impact of alpha-N-acetylation on structural and functional status of parvalbumin.
abstract: The effect of alpha-N-acetylation (Nt-acetylation) on the properties of parvalbumin (PA), a Ca2+-binding relaxing factor of skeletal muscles and major food allergen, has been explored. Intact PA contains an N-terminal acetyl group which is absent in the protein expressed in Escherichia coli (rWT), as confirmed by mass spectrometry. Compared to intact pike α-PA, its rWT form exhibits essentially altered profile of thermal unfolding, lowered α-helicity, and decreased affinities to Ca2+ and Mg2+. The structural destabilization of the rWT protein results in lowered resistance to chymotryptic digestion and increased propensity to oligomerization. The rate constants of Ca2+ dissociation from the rWT PA are markedly increased, which indicates that Nt-acetylation modifies functional status of the protein. Rat α-PA demonstrates similar properties for intact and rWT forms. The drastic difference in the effects induced by Nt-acetylation in the PA orthologs can be rationalized by higher disorder level of AB domain in pike PA. Though evolution of PA's genes resulted in the protein sequences with highly divergent properties, Nt-acetylation unifies their functional properties. The structural stability conferred to PA by Nt-acetylation may contribute to its allergenicity. Overall, Nt-acetylation is shown to be a prerequisite for maintenance of structural and functional status of some parvalbumins.
authors: Institute for Biological Instrumentation of the Russian Academy of Sciences, Pushchino, Moscow region, 142290 Russia. permyakov.s@gmail.com
authors: Sergei E
authors: SE
authors: Permyakov
authors: Alisa A
authors: AA
authors: Vologzhannikova
authors: Victor I
authors: VI
authors: Emelyanenko
authors: Ekaterina L
authors: EL
authors: Knyazeva
authors: Alexei S
authors: AS
authors: Kazakov
authors: Yulia S
authors: YS
authors: Lapteva
authors: Maria E
authors: ME
authors: Permyakova
authors: Andrei P
authors: AP
authors: Zhadan
authors: Eugene A
authors: EA
authors: Permyakov
mesh_terms: D000107:Acetylation; D000485:Allergens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002942:Circular Dichroism; D004926:Escherichia coli / Q000235:genetics*; D017859:Esocidae; D019143:Evolution, Molecular; D005512:Food Hypersensitivity / Q000276:immunology*; D006801:Humans; D013058:Mass Spectrometry; D009126:Muscle Relaxation / Q000502:physiology; D010320:Parvalbumins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017510:Protein Folding; D055503:Protein Multimerization; D055550:Protein Stability; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000485:Allergens; D010320:Parvalbumins; D011994:Recombinant Proteins; D002118:Calcium