Article
Biochemistry & Molecular Biology
Raju V. S. Rajala
Summary: The field of phosphoinositide signaling has expanded significantly in recent years, with phosphoinositides playing a crucial role in regulating various cellular functions. Recent studies have focused on PIP lipid signaling in the retina, highlighting the importance of investigating the function and mechanism of PIP-modifying enzymes/phosphatases in future research.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Lise C. Noack, Vincent Bayle, Laia Armengot, Frederique Rozier, Adiilah Mamode-Cassim, Floris D. Stevens, Marie-Cecile Caillaud, Teun Munnik, Sebastien Mongrand, Roman Pleskot, Yvon Jaillais
Summary: Phosphoinositides, specifically phosphatidylinositol 4-phosphate (PI4P), play a crucial role in membrane identity acquisition, particularly at the plant plasma membrane. PI4K alpha 1 is anchored to the plasma membrane through a complex involving proteins from various families, and is essential for pollen, embryonic, and post-embryonic development. The immobilization of the PI4K alpha 1 complex in plasma membrane nanodomains is critical for its function, highlighting the importance of lipid kinases in plasma membrane nanopatterning.
Review
Biochemistry & Molecular Biology
Kiae Kim, Yeonjin Han, Longhan Duan, Ka Young Chung
Summary: Beta-arrestins are proteins initially identified for desensitizing and internalizing G-protein-coupled receptors (GPCRs). By scaffolding MAPK signaling components, beta-arrestins initiate a second wave of signaling, promoting the activation of ERK1/2 or JNK3. Understanding the molecular and structural mechanisms of beta-arrestin-mediated MAPK scaffolding assembly is crucial for understanding GPCR-mediated MAPK activation and selectively regulating the MAPK signaling cascade for therapeutic purposes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Michelle America, Naguissa Bostaille, Marie Eubelen, Maud Martin, Didier Y. R. Stainier, Benoit Vanhollebeke
Summary: This study reveals the molecular mechanisms underlying the interactions between Gpr124 and Frizzled in zebrafish and mammals, and provides insights into the evolution of Gpr124/Reck function in vertebrates.
Article
Cell Biology
Alicia Llorente, Ryan M. Loughran, Brooke M. Emerling
Summary: Phosphoinositides play essential roles in cellular activities and their accurate measurement and identification pose challenges. Recent advances in techniques such as mass spectrometry, lipid biosensors, and fluorometric sensors have provided insights into the distribution and dynamics of phosphoinositides, highlighting their significance in human health and diseases, particularly cancer treatment. The exploration of phosphoinositide signaling not only deepens our understanding of cellular biology but also holds promise for novel interventions in cancer therapy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jie Zhang, Yijun Yang, Xinhua Li, Gen Li, Takuya Mizukami, Yanli Liu, Yuan Wang, Guoqiang Xu, Heinrich Roder, Li Zhang, Zeng-jie Yang
Summary: PDLIM3 plays a crucial role in ciliogenesis and hedgehog signaling transduction in SHH-MB cells, promoting cell proliferation and tumor growth. It can serve as a molecular marker for defining MB.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Cell Biology
Hanlin Ma, Fang Han, Xiaohui Yan, Gonghua Qi, Yingwei Li, Rongrong Li, Shi Yan, Cunzhong Yuan, Kun Song, Beihua Kong
Summary: Cervical cancer is the fourth most common cancer in women globally, and the overexpression of PBK in cervical cancer tissues promotes proliferation, metastasis, and cisplatin resistance of cancer cells through the ERK/c-Myc signaling pathway. Inhibition of PBK with OTS514 shows promising results in suppressing tumor growth and enhancing chemosensitivity. Further studies on PBK as a molecular target for cervical cancer treatment are warranted.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Tianmu Wen, Narendra Thapa, Vincent L. Cryns, Richard A. Anderson
Summary: Cytoplasmic phosphoinositides (PI) are crucial regulators of cellular functions. The metabolic cycle of different PI species plays a key role in their regulatory function. This review focuses on the evidence that scaffold proteins regulate the PI3K/Akt pathway in different membrane structures, challenging the belief that plasma membrane is the main site for PI3k/Akt signaling.
Article
Biochemistry & Molecular Biology
Jihyun Lee, Yujin Jung, Seo won Jeong, Ga Hee Jeong, Gue Tae Moon, Miri Kim
Summary: The Hippo signaling pathway and its effectors, YAP and TAZ, are found to play critical roles in angiogenesis and have potential therapeutic implications for rosacea. In a mouse model, inhibiting YAP and TAZ improved clinical features of rosacea and reduced VEGF immunoreactivity, suggesting their potential as therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lisa M. Rost, Synnove B. Raeder, Camilla Olaisen, Caroline K. Sogaard, Animesh Sharma, Per Bruheim, Marit Otterlei
Summary: The roles of PCNA as a scaffold protein in DNA replication and repair are well known, but its functions in the cytosol are less understood. ENO1 and 6PGD, two metabolic enzymes, interact with PCNA. Mutation of the PCNA interacting motif APIM in ENO1 resulted in reduced ENO1 protein levels, impaired growth rate, decreased glucose consumption, and reduced AKT activation. The interaction between PCNA and ENO1 has significant effects on metabolism.
Article
Biochemistry & Molecular Biology
Elise F. Tahti, Jadon M. Blount, Sophie N. Jackson, Melody Gao, Nicholas P. Gill, Sarah N. Smith, Nick J. Pederson, Simone N. Rumph, Sarah A. Struyvenberg, Iain G. P. Mackley, Dean R. Madden, Jeanine F. Amacher
Summary: Protein-protein interactions involving short peptide recognition play a critical role in cellular processes. Selectivity determinants can be challenging to dissect due to the small and shallow protein-peptide interaction surface areas and the overlapping specificities in families of peptide-binding domains. PDZ domains are peptide-binding domains found in intracellular signaling and trafficking pathways, and are also targeted by pathogens and oncogenic viral proteins. However, there is a wide spectrum of relative promiscuity among sequences that target PDZ domains. This study investigates the binding affinities and selectivity of PDZ domains for different peptide sequences and provides insights into the complexity of PDZ interactomes in cells.
Article
Chemistry, Physical
Benjamin S. Cowan, David L. Beveridge, Kelly M. Thayer
Summary: Allosteric signaling in proteins has been an active area of research, and the importance of electrostatics in long-range signaling has been increasingly recognized. This study focuses on the allosteric dynamics of the PDZ protein, utilizing molecular dynamics trajectories to create networks and exploring the allosteric effect. A new metric is introduced to quantify the volume sampled by a residue in the latent space, providing insights into PDZ and the field of allostery.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Cell Biology
Troy A. Kervin, Michael Overduin
Summary: The recognition of phosphatidylinositol phosphates (PIPs) by proteins plays a crucial role in cellular processes, with phosphorylation modification being a key regulatory mechanism. Analysis of protein structures and phosphoproteomic databases reveals that the regulation of membrane readers is essential for selective protein targeting to organelles.
Article
Gastroenterology & Hepatology
Ting Liu, Xiao-Li Xie, Xue Zhou, Sheng-Xiong Chen, Yi-Jun Wang, Lin-Ping Shi, Shu-Jia Chen, Yong-Juan Wang, Shu-Ling Wang, Jiu-Na Zhang, Shi-Ying Dou, Xiao-Yu Jiang, Ruo-Lin Cui, Hui-Qing Jiang
Summary: YB-1, overexpressed in HCC tissues, enhances sorafenib resistance through the PI3K/Akt pathway. Knockdown of YB-1 can improve the efficacy of sorafenib in vivo. The interaction between YB-1 and key proteins of the PI3K/Akt pathway contributes to sorafenib resistance in HCC.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Article
Cell Biology
Troy A. Kervin, Brittany C. Wiseman, Michael Overduin
Summary: Membrane readers participate in cellular trafficking and signaling pathways by interacting with specific lipid molecules, a process regulated by modifications of certain amino acid residues. These modifications, named MET-stops, are concentrated in the membrane binding sites of half of the PX domains in the human proteome and correlate with phosphoregulatory sites.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Johanna Kliche, Ylva Ivarsson
Summary: Cellular function relies on protein-protein interactions, which often involve the binding of short linear motifs by folded globular domains. These interactions are regulated by post-translational modifications like phosphorylation, which can alter motif binding sites or modulate interaction affinity. Understanding how these interactions work is crucial in determining the specificity and function of enzymes like serine/threonine kinases and phosphatases.
BIOCHEMICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Caroline Benz, Muhammad Ali, Izabella Krystkowiak, Leandro Simonetti, Ahmed Sayadi, Filip Mihalic, Johanna Kliche, Eva Andersson, Per Jemth, Norman E. Davey, Ylva Ivarsson
Summary: Specific protein-protein interactions are crucial for cell physiology, but many interactions are yet to be discovered. This study introduces an optimized peptide-phage display library that allows for the screening of numerous peptides in a single binding assay, aiding the discovery of SLiM-based interactions.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Norman E. Davey, Leandro Simonetti, Ylva Ivarsson
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Ylva Ivarsson
Article
Biology
Yitong Li, Vijaya Kumar Balakrishnan, Michael Rowse, Cheng-Guo Wu, Anastasia Phoebe Bravos, Vikash K. Yadav, Ylva Ivarsson, Stefan Strack, Irina Novikova, Yongna Xing
Summary: This study demonstrates that PME-1 can regulate different families of PP2A holoenzymes and block substrate recognition. The high-resolution cryoelectron microscopy structure reveals the binding mode of PME-1 with the B56 regulatory subunit and the selective impact on PP2A-B56 holoenzymes. The findings uncover multiple mechanisms of PME-1 in suppressing holoenzyme functions and versatile activities.
Article
Virology
Richard Lindqvist, Caroline Benz, Vita Sereikaite, Lars Maassen, Louise Laursen, Per Jemth, Kristian Stromgaard, Ylva Ivarsson, Anna K. Overby
Summary: A novel broad spectrum antiviral inhibitor targeting the PDZ1 domain of host protein syntenin has been discovered, which effectively inhibits the infection of RNA viruses such as SARS-CoV-2, chikungunya virus, and flavivirus.
Article
Biochemical Research Methods
Eszter Kassa, Sara Jamshidi, Filip Mihalic, Leandro Simonetti, Johanna Kliche, Per Jemth, Sara Bergstrom Lind, Ylva Ivarsson
Summary: In this study, biotinylated peptide pulldown and PRISMA coupled to mass spectrometry (MS) were evaluated and compared for discovery and validation of low affinity and transient protein-protein interactions. The results show that biotinylated peptide pulldown is more effective in validating SLiM-based interactions compared to PRISMA. The study provides insights for further method development.
ANALYTICAL BIOCHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Priyanka Madhu, Norman E. Davey, Ylva Ivarsson
Summary: Viruses exploit the host cellular machinery to replicate through interactions with host proteins, including recognition of host globular domains by short linear motifs or intrinsically disordered domains. This review focuses on the strategies used by viruses to bind to the disordered regions of human or viral ligands, including the use of viral domains and proteins. Protein-protein interactions are crucial for viral replication and may be targets for inhibitor design.
ESSAYS IN BIOCHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Leandro Simonetti, Jakob Nilsson, Gerald McInerney, Ylva Ivarsson, Norman E. Davey
Summary: SLiM-mediated interactions provide an unique strategy for viral intervention by mimicry of host SLiMs. Targeting commonly mimicked SLiMs could broaden the spectrum of antiviral drugs and improve our ability to handle viral outbreaks. In this opinion article, we advocate the therapeutic relevance of SLiMs as targets for broad-spectrum antiviral inhibitors.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Ali, Alisa Khramushin, Vikash K. Yadav, Ora Schueler-Furman, Ylva Ivarsson
Summary: The ERM family proteins and merlin participate in scaffolding and signaling events at the cell cortex. By screening the FERM domains of these proteins against a phage library, they discovered novel interaction motifs and binding sites. They defined distinct binding sites and provided a molecular understanding of how peptides with distinct motifs bind to different sites on the moesin FERM phosphotyrosine binding-like subdomain.
Article
Biochemistry & Molecular Biology
Norman E. Davey, Leandro Simonetti, Ylva Ivarsson
Summary: Short linear motifs (SLiMs) are unique and ubiquitous protein interaction modules that play important regulatory roles and drive dynamic complex formation. Recent methodological advances have enabled high-throughput discovery of SLiM-mediated interactome in the human cell, filling a significant blind spot in current interactomics data. This article discusses the key methods used to explore the elusive SLiM-mediated interactome and its implications for the field.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Johanna Kliche, Dimitriya Hristoforova Garvanska, Leandro Simonetti, Dilip Badgujar, Doreen Dobritzsch, Jakob Nilsson, Norman E. Davey, Ylva Ivarsson
Summary: Phosphorylation is a common post-translation modification that regulates protein function through protein-protein interactions. We created a phosphomimetic peptide-phage display library to discover phosphosites that modulate short linear motif-based interactions. Our research identified 248 phosphosites that modulate motif-mediated interactions, and we studied the phospho-dependent interaction between clathrin and HURP in detail. The structural characterization of the clathrin-HURP complex revealed the molecular basis for the phospho-dependency. Our work demonstrates the importance of phosphomimetic ProP-PD in discovering novel phospho-modulated interactions essential for cellular function.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Filip Mihalic, Leandro Simonetti, Girolamo Giudice, Marie Rubin Sander, Richard Lindqvist, Marie Berit Akpiroro Peters, Caroline Benz, Eszter Kassa, Dilip Badgujar, Raviteja Inturi, Muhammad Ali, Izabella Krystkowiak, Ahmed Sayadi, Eva Andersson, Hanna Aronsson, Ola Soderberg, Doreen Dobritzsch, Evangelia Petsalaki, Anna K. Overby, Per Jemth, Norman E. Davey, Ylva Ivarsson
Summary: Viruses hijack and deregulate cellular functions by mimicking host short linear motifs (SLiMs). In this study, a pan-viral approach is used to discover 1712 SLiM-based virus-host interactions, revealing novel host proteins hijacked by viruses and cellular pathways frequently deregulated. Furthermore, structural and biophysical analyses demonstrate that viral mimicry-based interactions have similar properties to endogenous interactions. The discovery of polyadenylate-binding protein 1 as a potential antiviral target highlights the therapeutic potential of this research in combating epidemics and pandemics.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Connor M. Blankenship, Jinshan Xie, Caroline Benz, Ao Wang, Ylva Ivarsson, Jiaoyang Jiang
Summary: Peptide phage display technique identifies the role of the intervening domain (Int-D) of O-GlcNAc transferase (OGT) in regulating protein-protein interactions and substrate modification. The study reveals the mode of OGT substrate recognition and provides insights into the biological function of the Int-D.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Muhammad Ali, Mishal Mariam McAuley, Susanne Luechow, Stefan Knapp, Andreas C. Joerger, Ylva Ivarsson
Summary: PDZ domains are a large family of modular domains known for binding C-terminal motifs of target proteins, but the interaction involving internal PDZ binding motifs (PDZbms) remains poorly studied. Using the PDZ domain of Shank1 as a model, this study explored internal PDZbm-mediated interactions, expanding the interactome of Shank1 and indicating a largely unexplored interaction space of PDZ domains. The findings revealed that both C-terminal and internal PDZbm interactions can occur in the context of full-length proteins, and the affinities of PDZbm interactions are in the low micromolar range.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2021)
