Review
Immunology
Yuqi Zhang, Ziran Qin, Wenhuan Sun, Feng Chu, Fangfang Zhou
Summary: Protein S-palmitoylation is a crucial lipid modification that regulates protein function in various biological processes. Recent studies have shown that palmitoylation plays significant roles in immune function by targeting immune-related proteins to the cellular membrane and lipid rafts. Aberrant protein acylation and changes in palmitoylation levels are linked to human immunologic diseases, making targeting palmitoylation a novel therapeutic approach for treating such disorders.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Charneal L. Dixon, Katrina Mekhail, Gregory D. Fairn
Summary: Phagocytosis is a process used by cells to engulf particles, with proteins modified by lipids to regulate signal transduction and immune functions. S-acylation, specifically S-palmitoylation, is a reversible modification that plays a role in regulating phagocytosis and phagosome biology in macrophages.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eric Soupene, Frans A. Kuypers
Summary: The transfer of acyl chains to proteins and lipids is achieved by ACBD6 and NMT enzymes, which play an essential role in protecting acyl donor from competitive inhibition. The absence of ACBD6/NMT complex leads to increased sensitivity to inhibitors and reduced myristoylation. ACBD6 also interacts with LPLAT enzymes, contributing to lipid acylation processes.
Review
Biochemistry & Molecular Biology
Keith T. Woodley, Mark O. Collins
Summary: Protein palmitoylation is important in cellular processes, with the palmitoyltransferase ZDHHC5 being a unique member of the PAT family that plays a vital role in different cell types. Recent research has revealed several mechanisms to control the activity, localization, and function of ZDHHC5.
Article
Biochemistry & Molecular Biology
Jarrett R. Remsberg, Radu M. Suciu, Noemi A. Zambetti, Thomas W. Hanigan, Ari J. Firestone, Anagha Inguva, Amanda Long, Nhi Ngo, Kenneth M. Lum, Cassandra L. Henry, Stewart K. Richardson, Marina Predovic, Ben Huang, Melissa M. Dix, Amy R. Howell, Micah J. Niphakis, Kevin Shannon, Benjamin F. Cravatt
Summary: The covalent inhibitor ABD957 selectively impairs N-Ras depalmitoylation in AML cells, showing potential as a targeted therapy for NRAS-mutant cancers. It acts on dynamically palmitoylated proteins at the plasma membrane, causing partial effects on N-Ras palmitoylation with greater proteome selectivity compared to Palmostatin M. Additionally, ABD957 inhibits N-Ras signaling and AML cell growth, synergizing with MEK inhibition.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Neurosciences
Busra P. Yucel, Enaam M. Al Momany, Ashley J. Evans, Richard Seager, Kevin A. Wilkinson, Jeremy M. Henley
Summary: The palmitoylation of GluK2 contributes to stabilizing the surface expression of KARs, while dynamic depalmitoylation promotes downstream phosphorylation and SUMOylation to mediate activity-dependent KAR endocytosis.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Biochemical Research Methods
Sachio Suzuki, Masaru Yoshikawa, Shunsuke Sawada, Neal K. Devaraj, Shinya Tsukiji
Summary: Conjugating small-molecule ligands to synthetic motifs that can localize to specific organelles or membranes is a practical approach to manipulate biological processes. We have developed a synthetic myristoyl-DCys motif that can undergo S-palmitoylation and localize to the Golgi surface. By miniaturizing the myristoyl-DCys motif, we have identified four new derivatives that retain the palmitoylation-dependent Golgi localization property. These miniaturized motifs can be used to generate small-molecule ligand conjugates for protein localization and cell signaling control.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Clinical Neurology
Gary P. H. Ho, Nagendran Ramalingam, Thibaut Imberdis, Erin C. Wilkie, Ulf Dettmer, Dennis J. Selkoe
Summary: The study demonstrated that inhibiting depalmitoylase acyl-protein-thioesterase-1 (APT1) can reduce alpha-synuclein (αS) cytoplasmic inclusions and alpha S-dependent neurotoxicity, while maintaining the palmitoylation level of the protein MAP6. This reveals a novel link between palmitoylation and αS pathophysiology, suggesting upregulating palmitoylation as a potential therapeutic strategy for synucleinopathies.
MOVEMENT DISORDERS
(2021)
Review
Biochemical Research Methods
Yang Wang, Wei Yang
Summary: Protein S-acylation, also known as palmitoylation, is a crucial reversible lipid modification that regulates protein functions. Recent advances in proteomic analysis of S-acylation have significantly improved our understanding of its biological processes. This research field is expected to play a key role in discovering new disease mechanisms and therapeutic targets.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Jozsef Gal, Vimala Bondada, Charles B. Mashburn, David W. Rodgers, Dorothy E. Croall, James W. Geddes
Summary: CAPN5 is a calcium-activated neutral thiol protease that is partly membrane associated. S-acylation of CAPN5 is critical for its membrane localization and enzymatic activity.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2022)
Article
Cell Biology
Anuttoma Ray, Parmender P. Mehta
Summary: Cx32 was found to be palmitoylated at cysteine 217 (C217) in cell line derived from prostate tumors, but mutating C217 to alanine had no effect on its function. Mutation of cysteine 280 and 283, only in combination, blocked the trafficking of Cx32 from the trans-Golgi network to the cell surface, leading to reduced stability.
CELLULAR SIGNALLING
(2021)
Article
Biochemistry & Molecular Biology
Emma H. Garst, Hwayoung Lee, Tandrila Das, Shibani Bhattacharya, Avital Percher, Rafal Wiewiora, Isaac P. Witte, Yumeng Li, Tao Peng, Wonpil Im, Howard C. Hang
Summary: Site-specific S-palmitoylation of IFITM3 enhances its antiviral activity by modulating its conformation and interaction with lipid membranes, demonstrating the direct impact of lipidation on the protein's biophysical properties and cellular activity to prevent virus infection.
ACS CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Irina Panina, Nikolay Krylov, Mohamed Rasheed Gadalla, Elena Aliper, Larisa Kordyukova, Michael Veit, Anton Chugunov, Roman Efremov
Summary: Lipid modification of viral proteins plays a crucial role in virus pathogenesis. The study focuses on human DHHC20 enzyme involved in S-protein acylation of SARS-CoV-2. Molecular dynamics simulations reveal that C16 is the preferred acyl chain length for autoacylation by hDHHC20, although the V185G mutant shows preference for C18. Unusual hydrophilic ridge and responsive hydrophilic patch in hDHHC20 and S-protein TM-domain trimer respectively are also found. Mutations in critical residues of the spike protein result in decreased S-acylation. The findings may contribute to the development of inhibitors targeting hDHHC20 for interfering with replication of coronaviruses and other enveloped viruses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Marilyn D. Resh
Summary: Fatty acylation is a crucial protein modification that affects protein affinity, signaling pathways, and cellular functions. Research in this field offers new therapeutic opportunities for targeting human diseases.
Review
Biochemistry & Molecular Biology
Martin Ian P. Malgapo, Maurine E. Linder
Summary: Protein palmitoylation is a post-translational modification method associated with various diseases, and identifying the protein substrates of zDHHC proteins is key to understanding their physiological and pathophysiological importance.
Article
Biochemistry & Molecular Biology
Kimon Lemonidis, Martin W. Werno, Jennifer Greaves, Cinta Diez-Ardanuy, Maria C. Sanchez-Perez, Christine Salaun, David M. Thomson, Luke H. Chamberlain
BIOCHEMICAL SOCIETY TRANSACTIONS
(2015)
Article
Neurosciences
Christine Salaun, Louise Ritchie, Jennifer Greaves, Trevor J. Bushell, Luke H. Chamberlain
MOLECULAR AND CELLULAR NEUROSCIENCE
(2017)
Article
Multidisciplinary Sciences
Jennifer Greaves, Kevin R. Munro, Stuart C. Davidson, Matthieu Riviere, Justyna Wojno, Terry K. Smith, Nicholas C. O. Tomkinson, Luke H. Chamberlain
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2017)
Article
Spectroscopy
Lauren E. Jamieson, Jennifer Greaves, Jayde A. McLellan, Kevin R. Munro, Nicholas C. O. Tomkinson, Luke H. Chamberlain, Karen Faulds, Duncan Graham
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2018)
Article
Biochemistry & Molecular Biology
Luke H. Chamberlain, Kimon Lemonidis, Maria Sanchez-Perez, Martin W. Werno, Oforiwa A. Gorleku, Jennifer Greaves
BIOCHEMICAL SOCIETY TRANSACTIONS
(2013)
Article
Biochemistry & Molecular Biology
Jennifer Greaves, Kimon Lemonidis, Oforiwa A. Gorleku, Carlos Cruchaga, Christopher Grefen, Luke H. Chamberlain
JOURNAL OF BIOLOGICAL CHEMISTRY
(2012)
Article
Cell Biology
Linda Sutherland, Madeleine Ruhe, Daniela Gattegno-Ho, Karanjit Mann, Jennifer Greaves, Magdalena Koscielniak, Stephen Meek, Zen Lu, Martin Waterfall, Ryan Taylor, Anestis Tsakiridis, Helen Brown, Sutherland K. Maciver, Anagha Joshi, Michael Clinton, Luke H. Chamberlain, Austin Smith, Tom Burdon
JOURNAL OF CELL SCIENCE
(2018)
Article
Cell Biology
Khamal K. Ampah, Jennifer Greaves, Amber S. Shun-Shion, Asral W. Asnawi, Jessica A. Lidster, Luke H. Chamberlain, Mark O. Collins, Andrew A. Peden
JOURNAL OF CELL SCIENCE
(2018)
Editorial Material
Oncology
Jennifer Greaves, Luke H. Chamberlain
JOURNAL OF PATHOLOGY
(2014)
Article
Cell Biology
Loic Fort, Jose Miguel Batista, Peter A. Thomason, Heather J. Spence, Jamie A. Whitelaw, Luke Tweedy, Jennifer Greaves, Kirsty J. Martin, Kurt I. Anderson, Peter Brown, Sergio Lilla, Matthew P. Neilson, Petra Tafelmeyer, Sara Zanivan, Shehab Ismail, David M. Bryant, Nicholas C. O. Tomkinson, Luke H. Chamberlain, Grant S. Mastick, Robert H. Insall, Laura M. Machesky
NATURE CELL BIOLOGY
(2018)
Article
Multidisciplinary Sciences
Cinta Diez-Ardanuy, Jennifer Greaves, Kevin R. Munro, Nicholas C. O. Tomkinson, Luke H. Chamberlain
SCIENTIFIC REPORTS
(2017)
Article
Biochemistry & Molecular Biology
Christine Salaun, Jennifer Greaves, Nicholas C. O. Tomkinson, Luke H. Chamberlain
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
News Item
Biochemistry & Molecular Biology
Jennifer Greaves
Summary: Acyl protein thioesterases play a critical role in regulating S-acylation by removing acyl chains from proteins. A cytosolic deacylase, APT2, is S-acylated by zDHHC3 and zDHHC7, and is involved in deforming the lipid bilayer to extract acyl chains and capture them within a hydrophobic pocket.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Tiina J. Ahonen, Choa P. Ng, Beatriz Farinha, Barbara Almeida, Bruno L. Victor, Christopher Reynolds, Eija Kalso, Jari Yli-Kauhaluoma, Jennifer Greaves, Vania M. Moreira
Summary: This study identified a class of highly selective inhibitors that can differentiate the inhibition of one enzyme from another. The structure-activity relationships presented here may inspire future drug discovery efforts in this field.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Review
Biochemistry & Molecular Biology
Kimon Lemonidis, Christine Salaun, Marianna Kouskou, Cinta Diez-Ardanuy, Luke H. Chamberlain, Jennifer Greaves
BIOCHEMICAL SOCIETY TRANSACTIONS
(2017)