Uncovering domain motif interactions using high ‐throughput protein–protein interaction detection methods
Protein –protein interactions (PPIs), often mediated by short linear motifs (SLiMs), shape cellular functions. This review provides an overview of SLiMs, and scrutinises current PPI detection techniques, highlighting their relevance to SLiM-mediated interactions and addressing challenges in detecting doma in–motif interactions (DMIs). Case studies, like BioGrid database analysis, suggest high-throughput PPI methods as reliable sources for predicting DMIs, enriching our understanding of cellular dynamics. Protein –protein interactions (PPIs) are often mediated by short linear motifs (SLiMs) in one protein and domain i...
Source: FEBS Letters - March 5, 2024 Category: Biochemistry Authors: Sobia Idrees,
Keshav Raj Paudel,
Tayyaba Sadaf,
Philip M. Hansbro Tags: Review Source Type: research
A life ‐time of hematopoietic cell function: ascent, stability, and decline
Here we review the aging of the hematopoietic system from its earliest stages in the embryo through fetal and adult life. We focus on the waves of hematopoietic cell generation during embryonic life and how cells of varying lineages, functions and life spans contribute to the normal development of the adult blood system and its progressive gain/loss of function in the aged adult. Aging is a set of complex processes that occur temporally and continuously. It is generally a unidirectional progression of cellular and molecular changes occurring during the life stages of cells, tissues and ultimately the whole organism. In ver...
Source: FEBS Letters - March 5, 2024 Category: Biochemistry Authors: Anna Popravko,
Lorna Mackintosh,
Elaine Dzierzak Tags: Review Source Type: research
Assessment of machine ‐learning predictions for the Mediator complex subunit MED25 ACID domain interactions with transactivation domains
In this study, we report a systematic assessment of AlphaFold performance to predict 9 different human MED25 ACID domain –transactivation domain (TAD) interfaces and evaluate the accuracy of the models through comparison with published and new experimental data. We also reveal a new interaction surface unique to plants by predicting 3 differentArabidopsis thaliana MED25 complexes. The human Mediator complex subunit MED25 binds transactivation domains (TADs) present in various cellular and viral proteins using two binding interfaces, named H1 and H2, which are found on opposite sides of its ACID domain. Here, we use and c...
Source: FEBS Letters - March 4, 2024 Category: Biochemistry Authors: Didier Mont é,
Zoé Lens,
Frédérique Dewitte,
Vincent Villeret,
Alexis Verger Tags: Research Article Source Type: research
The extremophilic Andean isolate Acinetobacter sp. Ver3 expresses two ferredoxin ‐NADP+ reductase isoforms with different catalytic properties
Extremophilic microorganisms are an invaluable source of new biomolecules with unique characteristics. The genome ofAcinetobacter sp. Ver3 isolated from high-altitude Andean lakes encodes two ferredoxin/flavodoxin-NADP+ oxidoreductases, FPR1ver3 and FPR2ver3, which display kinetic and spectroscopic characteristics similar to other prokaryotic FPRs and contribute to the bacterial protection against oxidative stress. Ferredoxin/flavodoxin-NADPH reductases (FPRs) catalyze the reversible electron transfer between NADPH and ferredoxin/flavodoxin. TheAcinetobacter sp. Ver3 isolated from high-altitude Andean lakes contains two is...
Source: FEBS Letters - March 4, 2024 Category: Biochemistry Authors: Alejandro Palavecino,
Mariana Gabriela Sartorio,
N éstor Carrillo,
Néstor Cortez,
Ana Bortolotti Tags: Research Article Source Type: research
How CBX proteins regulate normal and leukemic blood cells
We describe how CBX proteins dictate age-related changes in HSCs and stimulate oncogenic HSC fate decisions, either as canonical PRC1 members or by alternative interactions, including non-epigenetic regulation. CBX2, CBX7, and CBX8 enhance leukemia progression. To target, reprogram, and kill leukemic cells, we suggest and describe multiple therapeutic strategies to interfere with the epigenetic functions of oncogenic CBX proteins. Future studies should clarify to what extent the non-epigenetic function of cytoplasmic CBX proteins is important for normal, aged, and leukemic blood cells. (Source: FEBS Letters)
Source: FEBS Letters - March 1, 2024 Category: Biochemistry Authors: Anne P. de Groot,
Gerald de Haan Tags: Review Source Type: research
Crystal structure and solution scattering of Geobacillus stearothermophilus S9 peptidase reveal structural adaptations for carboxypeptidase activity
Acylaminoacyl peptidases (AAPs) are implicated in cancer and neurological disorders. The current research work investigates the structure –activity of a putative AAP fromGeobacillus stearothermophilus. Our study encompasses enzymatic, biophysical, structural, and solution scattering analyses. The crystal structure revealed the structural adaptations facilitating carboxypeptidase activity, and solution scattering confirms its quaternary structure. Acylaminoacyl peptidases (AAPs) play a pivotal role in various pathological conditions and are recognized as potential therapeutic targets. AAPs exhibit a wide range of activiti...
Source: FEBS Letters - March 1, 2024 Category: Biochemistry Authors: Khileshwari Chandravanshi,
Rahul Singh,
Gauri N. Bhange,
Ashwani Kumar,
Pooja Yadav,
Amit Kumar,
Ravindra D. Makde Tags: Research Letter Source Type: research
Plasmodium falciparum J ‐dot localized J domain protein A8iJp modulates the chaperone activity of human HSPA8
We report on a type-IV J domain protein (JDP), PF3D7_1401100, which we found to be processed before export and trafficked inside the lumen of parasite-derived structures known as J-dots. We found this protein to have holdase activity, as well as stimulate the ATPase and aggregation suppression activity of the human HSP70 chaperone HsHSPA8; thus, we named it “HSPA8-interacting J protein” (A8iJp). Moreover, we found a subset of HsHSPA8 to co-localize with A8iJp inside the infected human erythrocyte. Our results suggest that A8iJp modulates HsHSPA8 chaperone activity and may play an important role in host erythrocyte reno...
Source: FEBS Letters - February 29, 2024 Category: Biochemistry Authors: Welka Sahu,
Tapaswini Bai,
Aleena Das,
Subhadip Mukherjee,
Aradhana Prusty,
Nipa Rani Mallick,
Selvakumar Elangovan,
K. Sony Reddy Tags: Research Article Source Type: research
Resveratrol and its metabolites elicit neuroprotection via high ‐affinity binding to the laminin receptor at low nanomolar concentrations
In this study, based on the quenching of intrinsic tryptophan fluorescence and molecular docking, we found thattrans-resveratrol, its conjugates (glucuronide and sulfate), and dihydro-resveratrol (intestinal microbial metabolite) bind with high affinities (Kd, 0.2 –2 nm) to the peptide G palindromic sequence (near glycosaminoglycan-binding motif) of the 67-kDa laminin receptor (67LR). Preconditioning with low concentrations (0.01 –10 nm) of these polyphenols, especially resveratrol-glucuronide, protected neuronal cells from death induced by serum withdrawalvia activation of cAMP-mediated signaling pathways. This pr...
Source: FEBS Letters - February 29, 2024 Category: Biochemistry Authors: Rayudu Gopalakrishna,
Jennifer Aguilar,
Andrew Oh,
Emily Lee,
Lucas Hou,
Tammy Lee,
Eric Xu,
James Nguyen,
William J. Mack Tags: Research Letter Source Type: research
MATR3 pathogenic variants differentially impair its cryptic splicing repression function
MATR3 is a splicing regulator implicated in neurodegenerative and neurodevelopmental diseases, but its role in cryptic splicing repression within functional genes is unclear. Here, we show that MATR3 loss leads to cryptic exon inclusion in many functional genes. We also show that two disease-associated variants differentially affect MATR3 properties, solubility, and RNA binding, thereby impacting its cryptic splicing repression function. Matrin-3 (MATR3) is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within ...
Source: FEBS Letters - February 27, 2024 Category: Biochemistry Authors: Mashiat Khan,
Xiao Xiao Lily Chen,
Michelle Dias,
Jhune Rizsan Santos,
Sukhleen Kour,
Justin You,
Rebekah van Bruggen,
Mohieldin M. M. Youssef,
Ying ‐Wooi Wan,
Zhandong Liu,
Jill A. Rosenfeld,
Qiumin Tan,
Udai Bhan Pandey,
Hari Krishna Yala Tags: Research Article Source Type: research
