scholarly journals Identification and Characterization of a New Class of Trafficking Motifs for Controlling Clathrin-independent Internalization and Recycling

2007 ◽  
Vol 282 (17) ◽  
pp. 13087-13097 ◽  
Author(s):  
Qiang Gong ◽  
Michael Weide ◽  
Christopher Huntsman ◽  
Zhuojin Xu ◽  
Lily Y. Jan ◽  
...  
2017 ◽  
Vol 58 (14) ◽  
pp. 6500 ◽  
Author(s):  
Shu-Jie Zhang ◽  
Xue Chen ◽  
Chao-Peng Li ◽  
Xiu-Miao Li ◽  
Chang Liu ◽  
...  

2021 ◽  
Author(s):  
Norbert S. Hill ◽  
Matthew D. Welch

Mycobacterium marinum, a close relative of the significant human pathogen Mycobacterium tuberculosis, polymerizes host actin at the bacterial surface to drive intracellular movement and cell-to-cell spread during infection. Here, we report the identification and characterization of MirA, the M. marinum actin-based motility factor. MirA is a member of the glycine-rich PE_PGRS family of ESX-5-secreted proteins. MirA uses an amphipathic helix to anchor into the mycobacterial outer membrane and, surprisingly, also the surface of host lipid droplet organelles. The glycine-rich PGRS domain in MirA directly binds and activates host N-WASP to stimulate actin polymerization through the Arp2/3 complex, directing both bacterial and lipid droplet actin-based motility. MirA is dissimilar to known N-WASP activating ligands and may represent a new class of microbial and host actin regulator. Additionally, the MirA-N-WASP interaction represents a model to understand how the enigmatic PE_PGRS proteins contribute to mycobacterial pathogenesis.


Biochemistry ◽  
2019 ◽  
Vol 58 (43) ◽  
pp. 4352-4360 ◽  
Author(s):  
Ugur Meric Dikbas ◽  
Mehmet Tardu ◽  
Asena Canturk ◽  
Seref Gul ◽  
Gozde Ozcelik ◽  
...  

2019 ◽  
Author(s):  
Yoshitaka Sakamoto ◽  
Liu Xu ◽  
Masahide Seki ◽  
Toshiyuki T. Yokoyama ◽  
Masahiro Kasahara ◽  
...  

AbstractHere we report identification of a new class of local structural aberrations in lung cancers. The whole-genome sequencing of cell lines using a long read sequencer, PromethION, demonstrated that typical cancerous mutations, such as point mutations, large deletions and gene fusions can be detected also on this platform. Unexpectedly, we revealed unique structural aberrations consisting of complex combinations of local duplications, inversions and micro deletions. We further analyzed and found that these mutations also occur in vivo, even in key cancer-related genes. These mutations may elucidate the molecular etiology of patients for whom causative cancerous events and therapeutic strategies remain elusive.


PLoS ONE ◽  
2015 ◽  
Vol 10 (10) ◽  
pp. e0141214 ◽  
Author(s):  
Sebastian Memczak ◽  
Panagiotis Papavasileiou ◽  
Oliver Peters ◽  
Nikolaus Rajewsky

2006 ◽  
Vol 281 (26) ◽  
pp. 17768-17778 ◽  
Author(s):  
Gaozhong Shen ◽  
Nicolle A. Saunée ◽  
Shervonda R. Williams ◽  
Eduardo F. Gallo ◽  
Wendy M. Schluchter ◽  
...  

2016 ◽  
Vol 113 (13) ◽  
pp. 3669-3674 ◽  
Author(s):  
Min-Suk Song ◽  
Gyanendra Kumar ◽  
William R. Shadrick ◽  
Wei Zhou ◽  
Trushar Jeevan ◽  
...  

The influenza endonuclease is an essential subdomain of the viral RNA polymerase. It processes host pre-mRNAs to serve as primers for viral mRNA and is an attractive target for antiinfluenza drug discovery. Compound L-742,001 is a prototypical endonuclease inhibitor, and we found that repeated passaging of influenza virus in the presence of this drug did not lead to the development of resistant mutant strains. Reduced sensitivity to L-742,001 could only be induced by creating point mutations via a random mutagenesis strategy. These mutations mapped to the endonuclease active site where they can directly impact inhibitor binding. Engineered viruses containing the mutations showed resistance to L-742,001 both in vitro and in vivo, with only a modest reduction in fitness. Introduction of the mutations into a second virus also increased its resistance to the inhibitor. Using the isolated wild-type and mutant endonuclease domains, we used kinetics, inhibitor binding and crystallography to characterize how the two most significant mutations elicit resistance to L-742,001. These studies lay the foundation for the development of a new class of influenza therapeutics with reduced potential for the development of clinical endonuclease inhibitor-resistant influenza strains.


2015 ◽  
Vol 60 (3) ◽  
pp. 1859-1861 ◽  
Author(s):  
Amy J. Jones ◽  
Marcel Kaiser ◽  
Vicky M. Avery

The screening of a focused library identified FTY720 (Fingolimod; Gilenya) as a potent selective antitrypanosomal compound active againstTrypanosoma brucei gambienseandT. brucei rhodesiense, the causative agents of human African trypanosomiasis (HAT). This is the first report of trypanocidal activity for FTY720, an oral drug registered for the treatment of relapsing multiple sclerosis, and the characterization of sphingolipids as a potential new class of compounds for HAT.


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