Intrinsic disorder of a nucleoplasmin ‐like histone chaperone specifies its discrete nuclear and nucleolar functions
All nucleoplasmin (NPM) proteins have large regions of intrinsic disorder, but it is not clear whether intrinsic disorder is an absolute requirement for all functions attributed to NPMs. We show that disordered regions of a yeast NPM-like protein, and lysine polyphosphorylation sites within them, are dispensable for NPM nucleolar functions, but key to NPM-mediated gene repression in the nucleus. Nucleoplasmin (NPM) histone chaperones regulate distinct processes in the nucleus and nucleolus. While intrinsically disordered regions (IDRs) are hallmarks of NPMs, it is not clear whether all NPM functions require these unstructu...
Source: FEBS Letters - December 11, 2023 Category: Biochemistry Authors: Courtney M. Gauthier, Josey LeGallais, Neda Savic, Sarah Moradi ‐Fard, Arden Grew, Martin Loe, Baran Kirlikaya, Jennifer Cobb, Christopher J. Nelson Tags: Research Letter Source Type: research

Intrinsic disorder of a nucleoplasmin ‐like histone chaperone specifies its discrete nuclear and nucleolar functions
All nucleoplasmin (NPM) proteins have large regions of intrinsic disorder, but It is not clear if intrinsic disorder is an absolute requirement for all functions attributed to NPMs. We show that disordered regions of a yeast NPM-like protein, and lysine polyphosphorylation sites within them, are dispensable for NPM nucleolar functions, but key to NPM-mediated gene repression in the nucleus. Nucleoplasmin (NPM) histone chaperones regulate distinct processes in the nucleus and nucleolus. While intrinsically disordered regions (IDRs) are hallmarks of NPMs, it is not clear if all NPM functions require these unstructured featur...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Courtney M. Gauthier, Josey LeGallais, Neda Savic, Sarah Moradi ‐Fard, Arden Grew, Martin Loe, Baran Kirlikaya, Jennifer Cobb, Christopher J. Nelson Tags: Research Letter Source Type: research

Human WIPI β‐propeller function in autophagy and neurodegeneration
Human WIPI β-propellers fulfill important functions in autophagy as phosphatidylinositol 3-phosphate effectors. The underlying scaffolding function is physiologically essential as WIPI mutations have dramatic effects on human health, particularly causing neurodegenerative diseases. The connection between WIPI mutations (A), the process of autophagy (B) and the neurodegenerative diseases (C) caused by WIPI mutations is given special attention in this review. The four human WIPI β-propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in the control of autophagy. In this contex...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Tassula Proikas ‐Cezanne, Maximilian L. Haas, Carmen J. Pastor‐Maldonado, David S. Schüssele Tags: In a Nutshell Source Type: research

Nonenzymatic RNA replication in a mixture of ‘spent’ nucleotides
In this study, we characterised the effect of a mixture of ‘spent’ nucleotides on template-directed nonenzymatic RNA replication, to understand how they might affect the reaction rates. Nonenzymatic template-directed replication would have been affected by co-solutes in a heterogenous prebiotic soup due to lack of enzymatic machinery. Unlike in contemporary biology, these reactions use chemically-activated nucleotides, which undergo rapid hydrolysis forming nucleoside monophosphates ( ‘spent’ monomers). These co-solutes cannot extend the primer but continue to base pair with the template, thereby interfering with r...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Gauri M. Patki, Sudha Rajamani Tags: Research Article Source Type: research

Human mitochondrial uncoupling protein 3 functions as a metabolite transporter
We show that recombinant human uncoupling protein 3 (UCP3), refolded and reconstituted into liposomes, efficiently transports aspartate and malate, and, to a lesser extent, phosphate and sulphate. Unlike UCP2, UCP3 cannot catalyse unidirectional substrate transport and exhibits an approximately sevenfold higher transport affinity for aspartate compared to UCP2. The R282Q mutation in the sixth α-helix completely abolishes the transport activity of UCP3. Since its discovery, a major debate about mitochondrial uncoupling protein 3 (UCP3) has been whether its metabolic actions result primarily from mitochondrial inner membran...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Francesco De Leonardis, Amer Ahmed, Angelo Vozza, Loredana Capobianco, Christopher L. Riley, Simona Nicole Barile, Daria Di Molfetta, Stefano Tiziani, John DiGiovanni, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte Tags: Research Letter Source Type: research

CRK and NCK adaptors may functionally overlap in zebrafish neurodevelopment, as indicated by common binding partners and overlapping expression patterns
This study finds CRK and NCK adaptors overlap in their neuronal expression during zebrafish development. It also finds CRK and NCK adaptors share common SH2 and SH3 binding partners from a neuronal cell line. Common binding partners include proteins critical for cell motility and adhesion. Together these data suggest CRK and NCK adaptors can play overlapping roles in neurodevelopment. CRK adaptor proteins are important for signal transduction mechanisms driving cell proliferation and positioning during vertebrate central nervous system development. Zebrafish lacking both CRK family members exhibit small, disorganized retin...
Source: FEBS Letters - December 7, 2023 Category: Biochemistry Authors: Helaina R. Stergas, Maeve Dillon ‐Martin, Caroline M. Dumas, Nicole A. Hansen, Francesca J. Carasi‐Schwartz, Alex R. D’Amico, Kylie M. Finnegan, Uatchet Juch, Keeley R. Kane, Isabel E. Kaplan, Madeline L. Masengarb, Marina E. Melero, Lau Tags: Research Article Source Type: research

Chemokine N ‐terminal‐derived peptides differentially regulate signaling by the receptors CCR1 and CCR5
In conclusion, chemokin e N termini can be mimicked to produce small CCR1-selective agonists, as well as CCR5-selective modulators. (Source: FEBS Letters)
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Olav Larsen, Sara Schuermans, Anna Walser, Stavroula Louka, Ida Aaberg Lillethorup, Jon V åbenø, Katrine Qvortrup, Paul Proost, Mette M. Rosenkilde Tags: Research Letter Source Type: research

Gly56 in the synthetic site of isoleucyl ‐tRNA synthetase confers specificity and maintains communication with the editing site
Isoleucyl-tRNA synthetase (IleRS) is crucial for isoleucine decoding in every cell. How IleRS discriminates against the smaller valine, preserving the accuracy of translation, is an important question. Here, we show that the strictly conserved Gly is a key for amino acid discrimination in synthetic site-based editing reactions. Interestingly, Gly, located in the synthetic site, modulates the affinity of the distant editing site. Isoleucyl-tRNA synthetase (IleRS) links isoleucine to cognate tRNAvia the Ile-AMP intermediate. Non-cognate valine is often mistakenly recognized as the IleRS substrate; therefore, to maintain the ...
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Morana Dulic, Nina Krpan, Ita Gruic ‐Sovulj Tags: Research Article Source Type: research

Human mitochondrial uncoupling protein 3 functions as a metabolite transporter
We show that recombinant human uncoupling protein 3 (UCP3), refolded and reconstituted into liposomes, efficiently transports aspartate and malate, and, to a lesser extent, phosphate and sulphate. Unlike UCP2, UCP3 cannot catalyse unidirectional substrate transport and exhibits an approximately sevenfold higher transport affinity for aspartate compared to UCP2. The R282Q mutation in the sixth α-helix completely abolishes the transport activity of UCP3. Since its discovery, a major debate about mitochondrial uncoupling protein 3 (UCP3) has been whether its metabolic actions result primarily from mitochondrial inner membran...
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Francesco De Leonardis, Amer Ahmed, Angelo Vozza, Loredana Capobianco, Christopher L. Riley, Simona Nicole Barile, Daria Di Molfetta, Stefano Tiziani, John DiGiovanni, Luigi Palmieri, Vincenza Dolce, Giuseppe Fiermonte Tags: Research Letter Source Type: research

Human WIPI β‐propeller function in autophagy and neurodegeneration
Human WIPI β-propellers fulfill important functions in autophagy as phosphatidylinositol 3-phosphate effectors. The underlying scaffolding function is physiologically essential as WIPI mutations have dramatic effects on human health, particularly causing neurodegenerative diseases. The connection between WIPI mutations (A), the process of autophagy (B) and the neurodegenerative diseases (C) caused by WIPI mutations is given special attention in this review. The four human WIPI β-propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in the control of autophagy. In this contex...
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Tassula Proikas ‐Cezanne, Maximilian L. Haas, Carmen J. Pastor‐Maldonado, David S. Schüssele Tags: In a Nutshell Source Type: research

Gly56 in the synthetic site of isoleucyl ‐tRNA synthetase confers specificity and maintains communication with the editing site
Isoleucyl-tRNA synthetase (IleRS) is crucial for isoleucine decoding in every cell. How IleRS discriminates against the smaller valine, preserving the accuracy of translation, is an important question. Here, we show that the strictly conserved Gly is a key for amino acid discrimination in synthetic site-based editing reactions. Interestingly, Gly, located in the synthetic site, modulates the affinity of the distant editing site. Isoleucyl-tRNA synthetase (IleRS) links isoleucine to cognate tRNAvia the Ile-AMP intermediate. Non-cognate valine is often mistakenly recognized as the IleRS substrate; therefore, to maintain the ...
Source: FEBS Letters - December 6, 2023 Category: Biochemistry Authors: Morana Dulic, Nina Krpan, Ita Gruic ‐Sovulj Tags: Research Article Source Type: research

Reprogramming nucleolar size by genetic perturbation of the extranuclear Rab GTPases Ypt6 and Ypt32
Perturbation of genes encoding factors functioning in the nucleus and secretory pathway led to opposite effects on nucleolar size inSaccharomyces cerevisiae. We demonstrate evidence for reversing nucleolar hypertrophy by employing these two classes of mutations and the plausible involvement of Maf1 (the negative regulator of RNA polymerase III) in the process. Our study provides a prospective approach to reprogram the altered nucleolar size phenotype, a common feature of diseased cells. Reprogramming organelle size has been proposed as a potential therapeutic approach. However, there have been few reports of nucleolar size...
Source: FEBS Letters - December 2, 2023 Category: Biochemistry Authors: Shreosi Chatterjee, Abira Ganguly, Dibyendu Bhattacharyya Tags: Research Article Source Type: research

The role of lipid droplet associated proteins in inherited human disorders
Proteins which associate with the surface of lipid droplets are intimately involved in the regulation of the droplets. Several human inherited disorders have now been linked to loss- and, in some cases, likely gain-of-function mutations in the genes encoding these proteins. These are summarised in this Graphical Review. (Source: FEBS Letters)
Source: FEBS Letters - November 29, 2023 Category: Biochemistry Authors: Xiaowen Duan, David B. Savage Tags: Graphical Review Source Type: research