2VTX

ACTIVATION OF NUCLEOPLASMIN, AN OLIGOMERIC HISTONE CHAPERONE, CHALLENGES ITS STABILITY

Summary for 2VTX

• Entry DOI: 10.2210/pdb2vtx/pdb
• Descriptor: NPM-A PROTEIN (3 entities in total)
• Functional Keywords: nucleoplasmin, phosphorylation, protein stability, oligomeric protein, nuclear protein
• Biological source: XENOPUS LAEVIS (AFRICAN CLAWED FROG); More
• Total number of polymer chains: 10
• Total formula weight: 133853.73

Authors

Taneva, S.G.,Munoz, I.G.,Franco, G.,Falces, J.,Arregi, I.,Muga, A.,Montoya, G.,Urbaneja, M.A.,Banuelos, S. (deposition date: 2008-05-16, release date: 2008-12-16, Last modification date: 2023-12-13)

Primary citation

Taneva, S.G.,Munoz, I.G.,Franco, G.,Falces, J.,Arregi, I.,Muga, A.,Montoya, G.,Urbaneja, M.A.,Banuelos, S.
Activation of Nucleoplasmin, an Oligomeric Histone Chaperone, Challenges its Stability.
Biochemistry, 47:13897-, 2008

PubMed Abstract: Nucleoplasmin (NP) is a pentameric, ring-shaped histone chaperone involved in chromatin remodeling processes such as sperm decondensation at fertilization. Monomers are formed by a core domain, responsible for oligomerization, that confers the protein a high stability and compactness and a flexible tail domain, that harbors a polyglutamic tract and the nuclear localization signal. Fully activated NP presents multiple phosphorylated residues in the tail and in flexible regions of the core domain. In this work, we analyze the effect of activation on the structure and stability of the full-length protein and the isolated core domain through phosphorylation mimicking mutations. We have solved the crystal structure of an activated NP core domain that, however, is not significantly different from that of the wild-type,inactive, NP core. Nevertheless, we find that NP activation results in a strong destabilization of the pentamer probably due to electrostatic repulsion. Moreover, characterization of the hydrodynamic properties of both full-length and core domain proteins indicates that activating mutations lead to an expansion of the NP pentamer in solution. These findings suggest that NP needs a compact and stable structure to afford the accumulation of negative charges that weakens its quaternary interactions but is required for its biological function.

PubMed: 19055325
DOI: 10.1021/BI800975R

Experimental method

X-RAY DIFFRACTION (2.5 Å)