The impact of alpha-N-acetylation on structural and functional status of parvalbumin

Permyakov, Sergei E.; Vologzhannikova, Alisa A.; Emelyanenko, V. I.; Knyazeva, Ekaterina L.; Kazakov, Alexei S.; Lapteva, Yulia S.; Permyakova, Maria E.; Zhadan, Andrei P.; Permyakov, Eugene A.

doi:10.1016/j.ceca.2012.06.002

Cited by 27 publications

(19 citation statements)

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“…Aside from the above, NTA has been shown to affect protein function and/or activity in a variety of cases, including hemoglobin isoforms (Scheepens et al, 1995; Ashiuchi et al, 2005), phospholamban (PLB) (Starling et al, 1996), N-TIMPs (N-terminal inhibitory domains of TIMPs/inhibitors of metalloproteinases) (Van Doren et al, 2008), parvalbumin (Permyakov et al, 2012), melanocyte-stimulating hormone (MSH) in the barfin flounder ( Verasper moseri ) (Kobayashi et al, 2009), the contractile proteins actin and tropomyosin in fission and budding yeast (Polevoda et al, 2003; Singer and Shaw, 2003; Coulton et al, 2010) as well as the stress-induced carboxypeptidase Y inhibitor Tfs1p in yeast (Caesar and Blomberg, 2004). …”

Section: Introductionmentioning

confidence: 99%

The biological functions of Naa10 — From amino-terminal acetylation to human disease

Dörfel

Lyon

2015

Gene

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N-terminal acetylation (NTA) is one of the most abundant protein modifications known, and the N-terminal acetyltransferase (NAT) machinery is conserved throughout all Eukarya. Over the past 50 years, the function of NTA has begun to be slowly elucidated, and this includes the modulation of protein–protein interaction, protein-stability, protein function, and protein targeting to specific cellular compartments. Many of these functions have been studied in the context of Naa10/NatA; however, we are only starting to really understand the full complexity of this picture. Roughly, about 40% of all human proteins are substrates of Naa10 and the impact of this modification has only been studied for a few of them. Besides acting as a NAT in the NatA complex, recently other functions have been linked to Naa10, including post-translational NTA, lysine acetylation, and NAT/KAT-independent functions. Also, recent publications have linked mutations in Naa10 to various diseases, emphasizing the importance of Naa10 research in humans. The recent design and synthesis of the first bisubstrate inhibitors that potently and selectively inhibit the NatA/Naa10 complex, monomeric Naa10, and hNaa50 further increases the toolset to analyze Naa10 function.

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Section: Introductionmentioning

confidence: 99%

The biological functions of Naa10 — From amino-terminal acetylation to human disease

Dörfel

Lyon

2015

Gene

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“…Separately, there is increasing evidence that NTA can help to structurally stabilize α ‐helices, particularly in proteins containing an unstructured N‐ terminus (Shoemaker et al, ; Fairman et al, ; Doig et al, ; Greenfield et al, ; Jarvis et al, ; Fauvet et al, ; Kang et al, ; Kang et al, ; Permyakov et al, ). Additionally, protein function has been shown to be regulated by NTA in humans (Scheepens et al, ; Ashiuchi et al, ; Starling et al, ; Van Doren et al, ) and yeast (Polevoda et al, ; Singer & Shaw, ; Coulton et al, ; Caesar & Blomberg, ).…”

Section: Introductionmentioning

confidence: 99%

Proteomic and genomic characterization of a yeast model for Ogden syndrome

Dörfel

Han

Crain

et al. 2016

Yeast

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Naa10 is an Nα‐terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co‐translationally acetylates the α‐amino group of newly synthetized proteins as they emerge from the ribosome. Roughly 40–50% of the human proteome is acetylated by Naa10, rendering this an enzyme one of the most broad substrate ranges known. Recently, we reported an X‐linked disorder of infancy, Ogden syndrome, in two families harbouring a c.109 T > C (p.Ser37Pro) variant in NAA10. In the present study we performed in‐depth characterization of a yeast model of Ogden syndrome. Stress tests and proteomic analyses suggest that the S37P mutation disrupts Naa10 function and reduces cellular fitness during heat shock, possibly owing to dysregulation of chaperone expression and accumulation. Microarray and RNA‐seq revealed a pseudo‐diploid gene expression profile in ΔNaa10 cells, probably responsible for a mating defect. In conclusion, the data presented here further support the disruptive nature of the S37P/Ogden mutation and identify affected cellular processes potentially contributing to the severe phenotype seen in Ogden syndrome. Data are available via GEO under identifier GSE86482 or with ProteomeXchange under identifier PXD004923. © 2016 The Authors. Yeast published by John Wiley & Sons, Ltd.

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“…Separately, there is increasing evidence that NTA can help to structurally stabilize αhelices, particularly in proteins containing an unstructured N-terminus [14][15][16][17][18][19][20][21][22] . Additionally, protein targeted transformation (Supplemental Table 3: ON87/ON48).…”

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confidence: 99%

“…In conclusion, the data presented here further support the disruptive nature of the S37P/Ogden mutation and identify affected cellular processes, potentially contributing to the severe phenotype seen in Ogden syndrome. evidence that NTA can help to structurally stabilize -helices, particularly in proteins containing an unstructured N-terminus [14][15][16][17][18][19][20][21][22] . Additionally, protein function has been shown to be regulated by NTA in humans 23-26 and yeast [27][28][29][30] .…”

mentioning

confidence: 99%

Proteomic and Genomic Characterization of a Yeast Model for Ogden Syndrome

Doerfel

Han

Crain

et al. 2016

Preprint

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Naa10 is a N α -terminal acetyltransferase that, in a complex with its auxiliary subunit Naa15, co-translationally acetylates the α-amino group of newly synthetized proteins as they emerge from the ribosome. Roughly 40-50% of the human proteome is acetylated by Naa10, rendering this an enzyme with one of the most broad substrate ranges known. Recently, we reported an X-linked disorder of infancy, Ogden syndrome, in two families harboring a c.109T>C (p.Ser37Pro) variant in NAA10. In the present study we performed in-depth characterization of a yeast model of Ogden syndrome. Stress tests and proteomic analyses suggest that the S37P mutation disrupts Naa10 function thereby reducing cellular fitness, possibly due to an impaired functionality of molecular chaperones, Hsp104, Hsp40 and the Hsp70 family. Microarray and RNA-seq revealed a pseudodiploid gene expression profile in ΔNaa10 cells, likely responsible for a mating defect. In conclusion, the data presented here further support the disruptive nature of the S37P/Ogden mutation and identify affected cellular processes potentially contributing to the severe phenotype seen in Ogden syndrome.

show abstract

The impact of alpha-N-acetylation on structural and functional status of parvalbumin

Cited by 27 publications

References 89 publications

The biological functions of Naa10 — From amino-terminal acetylation to human disease

The biological functions of Naa10 — From amino-terminal acetylation to human disease

Proteomic and genomic characterization of a yeast model for Ogden syndrome

Proteomic and Genomic Characterization of a Yeast Model for Ogden Syndrome

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