2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
April 16th, 2025
Version: 1
Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf
biochemistry
biorxiv

Discovery of a new evolutionarily conserved short linear F-actin binding motif

Paraschiakos, T.Open in Google Scholar•Yuan, B.Open in Google Scholar•Sopelniak, K.Open in Google Scholar•Bucher, M.Open in Google Scholar•Simon, L.Open in Google Scholar•Zonjic, K.Open in Google Scholar•Eggers, D.Open in Google Scholar•Selle, F.Open in Google Scholar•Li, J.Open in Google Scholar•Linder, S.Open in Google Scholaret al.

Regulation of the actin cytoskeleton by actin binding proteins (ABPs) is essential for cellular homeostasis, and the mode of actin binding determines the activity of ABPs. Here, we discovered a novel Short linear F-actin binding motif (SFM) on the basis of the cryo-EM structure of the ITPKA-F-actin complex. We developed the computational pipeline SLiMFold, which identified 103 human SFM containing-proteins exhibiting diverse cellular functions. The SFM probably developed ex nihilo and remained conserved in eukaryotes, with a binding affinity to F-actin ranging from 13 to 89 micromolar. Furthermore, we uncovered the essential amino acids of this SFM for F-actin binding and affinity modulation. Together, the SFM seems to serve as a low affinity anchor to target proteins to F-actin, in order to connect the regulation of actin dynamics with broad cellular functions. These findings will shed new light on the role of a wide variety of proteins.

Similar Papers

biorxiv
Sun Apr 20 2025
Cellularly-Retained Fluorogenic Probes for Sensitive Cell-Resolved Bioactivity Imaging
Here, we develop a general design for high-quality fluorogenic activity probes to quantify biological processes in live cells, by creating a scaffold that efficiently generates cell-retained bright fluorescent soluble products upon reaction with biochemical targets. Live cell probes must be designed to be membrane-permeable; but that often means that their fluorophore products are similarly permea...
Mauker, P.
•
Dessen-Weissenhorn, L.
•
Zecha, C.
•
Veprek, N.
...•
Thorn-Seshold, O.
biorxiv
Sun Apr 20 2025
Improving Thermal and Gastric Stability of Phytase via pH Shifting and Coacervation: A Demonstration of Bayesian Optimization for Rapid Process Tuning
Phytase (phyA) breaks down phytate, which can help with nutrient absorption in a plant-based seed diet or high-phytate food. Unfortunately, it is prone to denaturation at food preparation temperatures and is easily inactivated by pepsin during gastric digestion. To protect phyA for use in high-temperature processes (100 ) and gastric digestion, chitosan (CS) was used to complex phyA. Bayesian opti...
Khongkomolsakul, W.
•
Buathong, P.
•
Yang, E.
•
Dadmohammadi, Y.
...•
Abbaspourrad, A.
biorxiv
Sun Apr 20 2025
Single-molecule microscopy reveals that TFIIE subunits dynamically interact with preinitiation complexes in a manner controlled by TFIIH
Transcription by RNA polymerase II (Pol II) requires general transcription factors that bind with Pol II at the promoters of protein-coding genes to form preinitiation complexes (PICs). Among these is TFIIE, which recruits TFIIH to the PIC and stimulates the kinase and translocase activities of TFIIH, thereby regulating the fate of formed PICs. In this study, we used a purified reconstituted human...
Archuleta, S. R.
•
Miller, R. C.
•
Mirita, J. A.
•
Goodrich, J. A.
•
Kugel, J. F.
biorxiv
Sun Apr 20 2025
Tandem Mass Tag-Based High-Resolution LC-MS/MS identifies free D-aspartate-induced expression of proteins linked to schizophrenia and autism spectrum disorder
D-aspartate is an endogenous agonist of NMDA and mGlu5 receptors, with a distinctive spatiotemporal expression profile that peaks in the prenatal and early postnatal brain. This suggests a critical role for D-aspartate metabolism in modulating neurodevelopmental processes linked to glutamatergic neurotransmission. However, the precise mechanisms through which D-aspartate exerts its effects remain ...
Errico, F.
•
Russo, R.
•
Carrillo, F.
•
Nuzzo, T.
...•
Chambery, A.
biorxiv
Sun Apr 20 2025
Plasma membrane transbilayer asymmetry of PI(4,5)P2 drives unconventional secretion of Fibroblast Growth Factor 2
Unconventional secretion of Fibroblast Growth Factor 2 (FGF2) is based upon direct self-translocation across the plasma membrane, a process that involves the transient formation of a lipidic membrane pore. The opening of this pore is triggered by PI(4,5)P2-dependent oligomerization of FGF2 at the inner plasma membrane leaflet. Subsequently, FGF2 oligomers populating the pore are captured by membra...
Kaur, M.
•
Lolicato, F.
•
Nickel, W.
biorxiv
Sun Apr 20 2025
Allosteric modulation of dimeric GPR3 by ligands in the dimerization interface
Class C G-protein coupled receptors (GPCRs) are widely recognized to function as a dimer, whereas the existence, molecular mechanisms and functional importance of dimerization in class A GPCRs remain poorly explored. GPR3, GPR6 and GPR12 are closely related to cannabinoid receptors, and are associated with neurogenerative diseases such as Parkinsons and Alzheimers diseases. Here, we determined cry...
Qiu, Z.
•
Wang, W.
•
Nie, Y.
•
Lin, J.
...•
Zheng, S.
biorxiv
Sat Apr 19 2025
The effect of fatty acid binding protein-3 exposure on endothelial transcriptomics
Background: Fatty acid binding protein-3 (FABP3) is released in circulation following myocardial infarction and an increased level of circulatory FABP3 is also reported in peripheral artery disease patients exposing endothelial cells to higher level of FABP3. Recently, loss of endothelial FABP3 was shown to protect endothelial cells against inflammation-induced endothelial dysfunction, however, th...
Nguyen, H. C.
•
Singh, A.
•
Castellani, C. A.
•
Qadura, M.
•
Singh, K. K.
biorxiv
Sat Apr 19 2025
Distinct mechanisms underlying extrachromosomal telomere DNA generation in ALT cancers
Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism observed in 15% of human cancers. A hallmark of ALT cancers is the presence of C-circles, circular single-stranded DNAs (ssDNAs) enriched with cytosine-rich telomere (C-rich, CCCTAA) sequences. G-circles, containing guanosine-rich telomere (G-rich, GGGTTA) ssDNAs, also exist but are much less abun...
Lee, J.
•
Sohn, E. J.
•
Lee, J.
•
Taglialatela, A.
...•
Min, J.
biorxiv
Sat Apr 19 2025
γ-Secretase-mediated endoproteolysis of neuregulin-1 and E-cadherin
{gamma}-Secretase is an intramembrane protease complex, with nearly 150 substrates that are cleaved within their transmembrane domains (TMD). Amyloid Precursor Protein (APP) is the most widely studied, as processive proteolysis by {gamma}{gamma}secretase releases the amyloid-{beta}-peptide implicated in the pathogenesis of Alzheimer's disease. In contrast, proteolysis of other substrates has been ...
Malvankar, S. R.
•
Wolfe, M. S.
biorxiv
Sat Apr 19 2025
Covalent targeting leads to the development of LIMK1 isoform-selective inhibitors
Selectivity for closely related isoforms of protein kinases is a major challenge in the design of drugs and chemical probes. Covalent targeting of unique cysteines is a potential strategy to achieve selectivity for highly conserved binding sites. Here, we used a pan-LIMK inhibitor to selectively probe LIMK1 over LIMK2 by targeting the LIMK1-specific cysteine C349 located in the glycine-rich loop r...
Mandel, S.
•
Hanke, T.
•
Prendiville, N.
•
Baena-Nuevo, M.
...•
Knapp, S.