Nucleoplasmin histone chaperone family
The diploid somatic cell contains roughly 2 meters of DNA within a nucleus of perhaps a few microns diameter; hence a fundamental problem exists in the packaging of DNA and subsequent read out of genetic information. Histone chaperones manage the protein building blocks of nucleosomes and thus, play pivotal roles in DNA replication and repair. Specialized chaperones store histones, decondense sperm chromatin after fertilization and help transfer histones onto DNA.
Nucleoplasmin (Np) family members are found in the animal lineage of higher eukaryotes and are present in oocytes, embryos and somatic cells. In Chordates, there are 3 major branches epitomized by Xenopus Np, NO38 and NO29. The conserved N-terminal domains of these chaperones form pentamers and contain a short stretch of acidic residues termed the A1 tract, which form an acidic crown on one face of the pentamer, while the C-terminal domains are variable and have either a single acidic tract (NO29/NPM3, dNLP) or multiple acidic tracts (Np, NO38/B23, ANO39 and Mp62). Family members also contain a basic region that may serve as an NLS to direct these chaperones to the nucleus. Np chaperones are able to bind histone dimers, tetramers or octamers; current models suggest that Np pentamers act like a gripping hand to bind histones with the acidic crown of A1-tracts and also use acidic tracts in their C-termini to form asymmetric complexes (Franco et al., 2019).
Selected Publications:
Dutta S, Akey IV, Dingwall C, Hartman KL, Laue T, Nolte RT, Head JF, Akey CW (2001). The crystal structure of nucleoplasmin-core: implications for histone binding and nucleosome assembly. Molecular Cell 841-53. doi: 10.1016/s1097-2765(01)00354-9. PMID: 11684019.
Namboodiri VM, Dutta S, Akey IV, Head JF, Akey CW (2003). The crystal structure of Drosophila NLP-core provides insight into pentamer formation and histone binding. Structure 11(2):175-86. doi: 10.1016/s0969-2126(03)00007-8. PMID: 12575937.
Namboodiri VM, Akey IV, Schmidt-Zachmann MS, Head JF, Akey CW. The structure and function of Xenopus NO38-core, a histone chaperone in the nucleolus. (2004). Structure 12(12):2149-60. doi: 10.1016/j.str.2004.09.017. PMID: 15576029.
Platonova O, Akey IV, Head JF, Akey CW (2011). Crystal structure and function of human nucleoplasmin (npm2): a histone chaperone in oocytes and embryos. Biochemistry 50(37):8078-89. doi: 10.1021/bi2006652. PMID: 21863821; PMCID: PMC3172369.
PubMed publications list
Nucleoplasmin family crystal structures:
Xenopus nucleoplasmin core: 1K5J
Drosophila NLP-core: 1NLQ
Human nucleoplasmin core: 3T30