Intrinsic disorder and multiple phosphorylations constrain the evolution of the flightin N-terminal region.

Abstract:

:Flightin is a myosin binding phosphoprotein that originated in the ancestor to Pancrustacea ~500 MYA. In Drosophila melanogaster, flightin is essential for length determination and flexural rigidity of thick filaments. Here, we show that among 12 Drosophila species, the N-terminal region is characterized by low sequence conservation, low pI, a cluster of phosphorylation sites, and a high propensity to intrinsic disorder (ID) that is augmented by phosphorylation. Using mass spectrometry, we identified eight phosphorylation sites within a 29 amino acid segment in the N-terminal region of D. melanogaster flightin. We show that phosphorylation of D. melanogaster flightin is modulated during flight and, through a comparative analysis to orthologs from other Drosophila species, we found phosphorylation sites that remain invariant, sites that retain the charge character, and sites that are clade-specific. While the number of predicted phosphorylation sites differs across species, we uncovered a conserved pattern that relates the number of phosphorylation sites to pI and ID. Extending the analysis to orthologs of other insects, we found additional conserved features in flightin despite the near absence of sequence identity. Collectively, our results demonstrate that structural constraints demarcate the evolution of the highly variable N-terminal region.

journal_name

J Proteomics

journal_title

Journal of proteomics

authors

Lemas D,Lekkas P,Ballif BA,Vigoreaux JO

doi

10.1016/j.jprot.2015.12.006

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

191-200

eissn

1874-3919

issn

1876-7737

pii

S1874-3919(15)30205-0

journal_volume

135

pub_type

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