Mutation of the small acidic tract A1 drastically reduces nucleoplasmin activity

Abstract

Xenopus laevis nucleoplasmin is a molecular chaperone that mediates sperm decondensation and nucleosome assembly. Nucleoplasmin has three acidic tracts (A1, A2 and A3) and until recent years the long polyglutamic tract A2 was thought to be the binding site for basic proteins. However, the latest publications in this field show that neither A2 nor A3 is indispensable for histone and sperm-specific protein binding. In this work, we show that the mutation of only four acidic amino acid residues of the small A1 tract drastically reduces nucleoplasmin decondensing activity, pointing out this region as the potential binding site for sperm proteins.

The intrinsically disordered distal face of nucleoplasmin recognizes distinct oligomerization states of histones

“…This domain has previously been proposed to exert a stabilizing role in NP-histone complex formation (29) and to increase 10 and 10 000 times the affinity of recombinant NP for H2A-H2B and H1, respectively (54). The A1 tract, a short loop with six acidic residues, acts synergistically with the C-terminal domain to bind core histones forming large complexes, similar to those seen in this study (45), and is involved in the decondensation activity of NP (81). …”

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

“…1). The shortest and the longest acidic regions are A1 and A3, respectively, in both species, which is similar to other nucleophosmins (Namboodiri et al 2004), whereas the longest acid region in nucleoplasmin is A2 (Salvany et al 2004). This provides further molecular structural evidence that our cloned nucleophosmin/ nucleoplasmin homologs are more closely related to nucleophosmin than to nucleoplasmin.…”

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

“…Complex formation results in charge neutralization, which in turn would stabilize it by diminishing the repulsion due to the proposed accumulation of negatively charged residues at the distal face of the NP pentamer (14,16,40). This negative patch would be formed by the acidic tracts A1, A2, and A3, and by the phosphoryl groups at the C-and N-terminal regions of the protein, not resolved in the x-ray structure of the core domain (17,20).…”