Function

Nucleoplasmin (Npl) is a molecular chaperone. Npl functions in the proper assembly of nucleosomes and chromatin structures^[1]. He is participates in histone storage, sperm chromatin decondensation, and nucleosome assembly,enome stability, ribosome biogenesis, DNA duplication and transcriptional regulation. In the assembly of nucleosomal arrays the NP transfer to DNA to him by binding the histones, this reaction requires ATP.

Relevance

Apoptotic chromatin condensation, one of the hallmarks of apoptosis, is regulated by Npl.

Structural highlights

Nucleoplasmin (NP) is made out of five ,that create ring-shaped histone chaperone. The monomers are formed by a that responsible for oligomerization, that make the protein highly stable and compact. The activation of NP is by strong destabilization of the pentamer, probably due to electrostatic repulsion. The NP needs compact and stable structure so he can accumulate negative charges that weakens its quaternary interactions, and its required for its biological function.

orthologey in Homo sapiens

the NP in Humans is made out of while each consisted of five chains. The structure remain similiar to the one in Xenopus but with a change in amino acids in its , Val insted of Ile. The Decamer bind H2A-H2B dimers and H3-H4 tetramers simultaneously, In the absence of histone tetramers the pentamer binds H2A-H2B and formes central hub. When H3-H4 tetramers are recruited this results in a functional dimerization of the complex, and the decamer being formed.

conservastion

Xenopus

Human

The general structure remain similiar, even with changes in amino acids in the core domains between the two species. That can point to the fact they have similar roles as a molecular chaperone in Human and Xenopus.

3D structures of nucleoplasmin

1k5j – XlNpl core – Xenopus laevis

2vtx - XlNpl core (mutant)

3t30 – Npl oligomerisation domain - human

1ee5, 1ejy –XlNpl nuclear localization peptide + karyopherin-a

3t30 - Human nucleoplasmin

References

1. ↑ Prado A, Ramos I, Frehlick LJ, Muga A, Ausio J. Nucleoplasmin: a nuclear chaperone. Biochem Cell Biol. 2004 Aug;82(4):437-45. PMID:15284896 doi:http://dx.doi.org/10.1139/o04-042

2. Taneva SG1, Muñoz IG, Franco G, Falces J, Arregi I, Muga A, Montoya G, Urbaneja MA, Bañuelos S. Activation of nucleoplasmin, an oligomeric histone chaperone, challenges its stability.Biochemistry. 2008 Dec 30;47(52):13897-906. PMID:19055325 DOI:10.1021/bi800975r

3. Dutta S1, Akey IV, Dingwall C, Hartman KL, Laue T, Nolte RT, Head JF, Akey CW. The crystal structure of nucleoplasmin-core: implications for histone binding and nucleosome assembly. Mol Cell.2001 Oct;8(4):841-53. PMID:11684019

4. SHU Te-Jun, ZHANG Yao-Zhou. Nucleoplasmin, an Important Nuclear Chaperone. Chinese Journal of Biochemistry and Molecular Biol. 15 March 2007 http://cjbmb.bjmu.edu.cn/EN/Y2007/V23/I09/718

5. Platonova, O., Akey, I.V., Head, J.F., Akey, C.W.Crystal structure and function of human nucleoplasmin (npm2): a histone chaperone in oocytes and embryos.Biochemistry.2011 Sep 20;50(37):8078-89.

PMCID:PMC3172369 DOI:10.1021/bi2006652