scholarly journals Coronavirus-Induced Membrane Fusion Requires the Cysteine-Rich Domain in the Spike Protein

Virology ◽  
2000 ◽  
Vol 269 (1) ◽  
pp. 212-224 ◽  
Author(s):  
Kevin W. Chang ◽  
YiWei Sheng ◽  
James L. Gombold
Keyword(s):  
Membrane Fusion ◽  
Spike Protein ◽  
Induced Membrane ◽  
Rich Domain ◽  
Cysteine Rich Domain

scholarly journals Inhibition of SARS-CoV-2 spike protein palmitoylation reduces virus infectivity

2021 ◽  
Author(s):  
Ahmed A. Ramadan ◽  
Karthick Mayilsamy ◽  
Andrew R. McGill ◽  
Anandita Ghosh ◽  
Marc A. Giulianotti ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Spike Protein ◽  
Virus Infectivity ◽  
Enveloped Viruses ◽  
Rich Domain ◽  
Protein Palmitoylation ◽  
Almost All ◽  
Precise Role ◽  
Cysteine Rich Domain

Spike glycoproteins of almost all enveloped viruses are known to undergo post-translational attachment of palmitic acid moieties. The precise role of such palmitoylation of the spike protein in membrane fusion and infection is not completely understood. Here, we report that palmitoylation of the first five cysteine residues of the c-terminal cysteine-rich domain of the SARS-CoV-2 spike are indispensable for infection, and palmitoylation deficient spike mutants are defective in trimerization and subsequent membrane fusion. The DHHC9 palmitoyltransferase interacts with and palmitoylates the spike protein in the ER and Golgi, and knockdown of DHHC9 results in reduced fusion and infection of SARS-CoV-2. Two bis-piperazine backbone-based DHHC9 inhibitors inhibit SARS-CoV-2 spike protein palmitoylation and the resulting progeny virion particles released are defective in fusion and infection. This establishes these palmitoyltransferase inhibitors as potential new intervention strategies against SARS-CoV-2.

scholarly journals The Evolution of the Scavenger Receptor Cysteine-Rich Domain of the Class A Scavenger Receptors

2015 ◽  
Vol 6 ◽  
Author(s):  
Nicholas V. L. Yap ◽  
Fiona J. Whelan ◽  
Dawn M. E. Bowdish ◽  
G. Brian Golding
Keyword(s):  
Scavenger Receptor ◽  
Scavenger Receptors ◽  
Class A ◽  
Rich Domain ◽  
Cysteine Rich Domain

scholarly journals The unusual structure of the PiggyMac cysteine-rich domain reveals zinc finger diversity in PiggyBac-related transposases

Mobile DNA ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marc Guérineau ◽  
Luiza Bessa ◽  
Séverine Moriau ◽  
Ewen Lescop ◽  
François Bontems ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Dna Cleavage ◽  
Trichoplusia Ni ◽  
Catalytic Domain ◽  
Structural Diversity ◽  
Paramecium Tetraurelia ◽  
Lysine Methylation ◽  
Unusual Structure ◽  
Rich Domain ◽  
Cysteine Rich Domain

Abstract Background Transposons are mobile genetic elements that colonize genomes and drive their plasticity in all organisms. DNA transposon-encoded transposases bind to the ends of their cognate transposons and catalyze their movement. In some cases, exaptation of transposon genes has allowed novel cellular functions to emerge. The PiggyMac (Pgm) endonuclease of the ciliate Paramecium tetraurelia is a domesticated transposase from the PiggyBac family. It carries a core catalytic domain typical of PiggyBac-related transposases and a short cysteine-rich domain (CRD), flanked by N- and C-terminal extensions. During sexual processes Pgm catalyzes programmed genome rearrangements (PGR) that eliminate ~ 30% of germline DNA from the somatic genome at each generation. How Pgm recognizes its DNA cleavage sites in chromatin is unclear and the structure-function relationships of its different domains have remained elusive. Results We provide insight into Pgm structure by determining the fold adopted by its CRD, an essential domain required for PGR. Using Nuclear Magnetic Resonance, we show that the Pgm CRD binds two Zn2+ ions and forms an unusual binuclear cross-brace zinc finger, with a circularly permutated treble-clef fold flanked by two flexible arms. The Pgm CRD structure clearly differs from that of several other PiggyBac-related transposases, among which is the well-studied PB transposase from Trichoplusia ni. Instead, the arrangement of cysteines and histidines in the primary sequence of the Pgm CRD resembles that of active transposases from piggyBac-like elements found in other species and of human PiggyBac-derived domesticated transposases. We show that, unlike the PB CRD, the Pgm CRD does not bind DNA. Instead, it interacts weakly with the N-terminus of histone H3, whatever its lysine methylation state. Conclusions The present study points to the structural diversity of the CRD among transposases from the PiggyBac family and their domesticated derivatives, and highlights the diverse interactions this domain may establish with chromatin, from sequence-specific DNA binding to contacts with histone tails. Our data suggest that the Pgm CRD fold, whose unusual arrangement of cysteines and histidines is found in all PiggyBac-related domesticated transposases from Paramecium and Tetrahymena, was already present in the ancestral active transposase that gave rise to ciliate domesticated proteins.

scholarly journals Elucidation of Binding Determinants and Functional Consequences of Ras/Raf-Cysteine-rich Domain Interactions

2000 ◽  
Vol 275 (29) ◽  
pp. 22172-22179 ◽  
Author(s):  
Jason G. Williams ◽  
Jonelle K. Drugan ◽  
Gwan-Su Yi ◽  
Geoffrey J. Clark ◽  
Channing J. Der ◽  
...  
Keyword(s):  
Rich Domain ◽  
Domain Interactions ◽  
Functional Consequences ◽  
Binding Determinants ◽  
Cysteine Rich Domain

scholarly journals A Functional F Analogue of Autographa californica Nucleopolyhedrovirus GP64 from the Agrotis segetum Granulovirus

2008 ◽  
Vol 82 (17) ◽  
pp. 8922-8926 ◽  
Author(s):  
Feifei Yin ◽  
Manli Wang ◽  
Ying Tan ◽  
Fei Deng ◽  
Just M. Vlak ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Membrane Fusion ◽  
Plutella Xylostella ◽  
Syncytium Formation ◽  
Low Ph ◽  
Autographa Californica ◽  
Agrotis Segetum ◽  
Induced Membrane ◽  
F Protein ◽  
Autographa Californica Nucleopolyhedrovirus

ABSTRACT The envelope fusion protein F of Plutella xylostella granulovirus is a computational analogue of the GP64 envelope fusion protein of Autographa californica nucleopolyhedrovirus (AcMNPV). Granulovirus (GV) F proteins were thought to be unable to functionally replace GP64 in the AcMNPV pseudotyping system. In the present study the F protein of Agrotis segetum GV (AgseGV) was identified experimentally as the first functional GP64 analogue from GVs. AgseF can rescue virion propagation and infectivity of gp64-null AcMNPV. The AgseF-pseudotyped AcMNPV also induced syncytium formation as a consequence of low-pH-induced membrane fusion.

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