Long-Term Evolution and Functional Diversification in the Members of the Nucleophosmin/Nucleoplasmin Family of Nuclear Chaperones

Abstract

The proper assembly of basic proteins with nucleic acids is a reaction that must be facilitated to prevent protein aggregation and formation of nonspecific nucleoprotein complexes. The proteins that mediate this orderly protein assembly are generally termed molecular (or nuclear) chaperones. The nucleophosmin/ nucleoplasmin (NPM) family of molecular chaperones encompasses members ubiquitously expressed in many somatic tissues (NPM1 and -3) or specific to oocytes and eggs (NPM2). The study of this family of molecular chaperones has experienced a renewed interest in the past few years. However, there is a lack of information regarding the molecular evolution of these proteins. This work represents the first attempt to characterize the long-term evolution followed by the members of this family. Our analysis shows that there is extensive silent divergence at the nucleotide level suggesting that this family has been subject to strong purifying selection at the protein level. In contrast to NPM1 and NPM-like proteins in invertebrates, NPM2 and NPM3 have a polyphyletic origin. Furthermore, the presence of selection for high frequencies of acidic residues as well as the existence of higher levels of codon bias was detected at the C-terminal ends, which can be ascribed to the critical role played by these residues in constituting the acidic tracts and to the preferred codon usage for phosphorylatable amino acids at these regions.

Molecular Characterization and Functional Commonality of Nucleophosmin/Nucleoplasmin in Two Cyprinid Fish

“…Moreover, immunodepletion and in vitro sperm decondensation experiments demonstrated a sperm decondensation function for these factors. These new findings are different from all previous studies on nucleophosmin/nucleoplasmin, in that nucleophosmin was observed to be expressed in somatic tissues and nucleoplasmin was revealed to be specific to oocytes and eggs in previous studies (Eirin-Lopez et al 2006;Shackleford et al 2001;Wedlich and Dreyer 1988). Our data suggest that Cag-nucleophosmin and Ca-nucleophosmin are nucleophosmin homologs but share expressional and functional commonalities with nucleoplasmin.…”

“…Their molecules contain acidic domains, multiple potential phosphorylation sites, and a putative nuclear localization signal (NLS) (Eirin-Lopez et al 2006), and their functions are multiple and diverse (Burns et al 2003).…”

Structural polymorphism in the N-terminal oligomerization domain of NPM1

“…The N-terminal structured domain mediates oligomerization and protein chaperone activity and contains two putative nuclear export signals (15). The central region, important for interactions with histones (25), is disordered (SI Appendix, Fig. S1A) and highly acidic, and contains a bipartite nuclear localization signal (15).…”

“…S1A) and highly acidic, and contains a bipartite nuclear localization signal (15). Last, the C-terminal domain, which evolved later and is not conserved in other members of the nucleoplasmin family (25), folds into a three-helix bundle (26,27), contains a nucleolar localization signal, and binds to nucleic acids (28). The NPM1 primary structure is highly conserved among mammals and amphibians (SI Appendix, Fig.…”

Nucleoplasmin Binds Histone H2A-H2B Dimers through Its Distal Face*

“…The nucleophosmin/nucleoplasmin family of histone chaperones is ubiquitously represented throughout the animal kingdom (4,12) and includes the following four main groups: nucleophosmin (NPM1), nucleoplasmin (NPM2 or NP), nucleoplasmin-like (NPM-like), and NPM3. All of them share similarities in their amino acid sequence.…”