Nucleobindin-2 consists of two structural components: The Zn2+-sensitive N-terminal half, consisting of nesfatin-1 and -2, and the Ca2+-sensitive C-terminal half, consisting of nesfatin-3

Bystranowska, Dominika; Skorupska, Anna; Sołtys, Katarzyna; Padjasek, Michał; Krężel, Artur; Żak, Andrzej; Kaus-Drobek, Magdalena; Taube, Michał; Kozak, Maciej; Ożyhar, Andrzej

doi:10.1016/j.csbj.2021.07.036

Cited by 6 publications

(22 citation statements)

References 119 publications

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“…Next, we tested the changes in secondary structure in the presence of Zn(II) and Ca(II), as their binding to the full-length protein has been reported [ 13 , 17 ]. We observed no effect of Ca(II) on nesfatin spectra, as shown in Additional file 1 : Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Since the binding of Zn(II) by the N-terminal fragment of hNucb2 [ 17 ] and Ca(II) by the C-terminal fragment [ 13 ] was reported, we decided to investigate the effects of those ions on the structure of nesfatins. In the first stage, we assessed the changes in the secondary structure in the presence of the above ions with CD spectroscopy.…”

Section: Discussionmentioning

confidence: 99%

“…It is also worth noting that the highly cooperative character of the binding curve of hN1/2 might result from the antagonistic mechanisms of hN1 and hN2 for Zn(II) binding and precipitation, respectively. This raises the question of whether Zn(II)-driven destabilization of hN1/2 and full-length hNucb2 [ 17 ] might be the effect of hN2-directed aggregation. Moreover, in silico studies of Nucb2 revealed that the aggregation prone region is located in the N-terminal segment, which was proven in this paper [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…This raises the question of whether Zn(II)-driven destabilization of hN1/2 and full-length hNucb2 [ 17 ] might be the effect of hN2-directed aggregation. Moreover, in silico studies of Nucb2 revealed that the aggregation prone region is located in the N-terminal segment, which was proven in this paper [ 17 ]. ZI competitive titration also proved the ability of hN1 to bind Zn(II), although the obtained K d was lower than expected, possibly due to a more complicated stoichiometry in the actual model.…”

Section: Discussionmentioning

confidence: 99%

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Does one plus one always equal two? Structural differences between nesfatin-1, -2, and nesfatin-1/2

et al. 2022

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Nesfatin-1 and -2 are produced from a reaction in which the N-terminus of human Nucleobindin-2 undergoes proteolytical processing. To date, Nucleobindin-2 and/or nesfatin-1 have only been shown to act as peptide hormones. On the other hand, the purpose of nesfatin-2 remains unknown. Since Nucleobindin-2/nesfatin-1 is thought impact the control of a wide range of physiological processes, including energy homeostasis, neurodegenerative processes and carcinogenesis, its ligands/interactions deserve special studies and attention. However, there are no reports about the molecular properties of the proteolytical products of human Nucleobindin-2 in the literature. Hence, this study aimed to analyze the effect of Zn(II) and Ca(II) on human nesfatin-1, -2, and -1/2 structures. Herein, we report that human nesfatin-1 is a member of the intrinsically disordered protein family, as indicated by circular dichroism and analytical ultracentrifugation experiments. In contrast, we found that the human nesfatin-2 and nesfatin-1/2 structures were globular with intrinsically disordered regions. Under Zn(II) treatment, we observed concentration-dependent structurization and compaction of intrinsically disordered nesfatin-1 and its propensity for oligomerization, as well as destabilization of both nesfatin-2 and nesfatin-1/2. Furthermore, dissociation constants for Zn(II) binding by nesfatin-1, nesfatin-2, and nesfatin-1/2 were also reported. Moreover, structurally distinct nesfatin-1 and -2 seem to be interdependent when linked together, as indicated by the observed molecular properties of nesfatin-1/2, which in turn are not a simple sum of the properties exhibited by the former peptides. Thus, herein, we shed new light on the molecular behavior of human nesfatins, which might help to elucidate the complex function of those peptides.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Does one plus one always equal two? Structural differences between nesfatin-1, -2, and nesfatin-1/2

et al. 2022

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“…NUCB2/NESF-1 is a pleiotropic peptide with many physiological functions [ 32 , 33 , 34 ]. Its metabolic function includes food intake, glucose metabolism, and the regulation of the immune, cardiovascular, and endocrine systems.…”

Section: Discussionmentioning

confidence: 99%

Expression of NUCB2/NESF-1 in Breast Cancer Cells

Kmiecik

Ratajczak‐Wielgomas²,

Grzegrzółka³

et al. 2022

IJMS

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Recently, the expression of NUCB2/NESF-1 has been linked to tumor development. We report NUCB2/NESF-1 expression and its relation to clinicopathological parameters in breast cancer cells. Immunohistochemical reactions were conducted on 446 cases of invasive ductal carcinoma (IDC) and 36 cases of mastopathy. The expression of NUCB2/NESF-1 was also examined at the mRNA and protein levels in breast cancer cell lines. A statistically significant higher level of NUCB2/NESF-1 in IDC cells was noted compared to that in mastopathy samples. The level of NUCB2 expression in the cytoplasm of IDC cells decreased with the increasing degree of tumor malignancy (G). Higher NUCB2 expression was found in tumors with estrogen receptor (ER)-positive and progesterone receptor (PR)-positive phenotypes compared to that in estrogen-receptor-negative and progesterone-receptor-negative cases. Moreover, a higher expression was shown in ER(+) and PR(+) MCF-7 and T47D cell lines compared to that in triple-negative MDA-MB-468 and normal human breast epithelial cells. The analysis of the five-year survival rate indicated that a positive NUCB2/NESF-1 expression in tumor cells was also associated with longer patient survival. The study results suggest that NUCB2/NESF1 may play an important role in malignant transformation and may be a positive prognostic factor in IDC.

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