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Minimal cobalt metabolism in the marine cyanobacterium Prochlorococcus 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (27) : 15740-15747
作者:  Hawco, Nicholas J.;  McIlvin, Matthew M.;  Bundy, Randelle M.;  Tagliabue, Alessandro;  Goepfert, Tyler J.;  Moran, Dawn M.;  Valentin-Alvarado, Luis;  DiTullio, Giacomo R.;  Saito, Mak A.
收藏  |  浏览/下载:19/0  |  提交时间:2020/06/29
Prochlorococcus  vitamin B12  iron  Pacific Ocean  nutrient limitation  
TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9 期刊论文
NATURE, 2020, 581 (7808) : 316-+
作者:  Kokail, C.;  Maier, C.;  van Bijnen, R.;  Brydges, T.;  Joshi, M. K.;  Jurcevic, P.;  Muschik, C. A.;  Silvi, P.;  Blatt, R.;  Roos, C. F.;  Zoller, P.
收藏  |  浏览/下载:35/0  |  提交时间:2020/07/03

The interaction between TASL and SLC15A4 links endolysosomal Toll-like receptors to the transcription factor IRF5, providing a mechanistic explanation for the involvement of the complex in systemic lupus erythematosus.


Toll-like receptors (TLRs) have a crucial role in the recognition of pathogens and initiation of immune responses(1-3). Here we show that a previously uncharacterized protein encoded by CXorf21-a gene that is associated with systemic lupus erythematosus(4,5)-interacts with the endolysosomal transporter SLC15A4, an essential but poorly understood component of the endolysosomal TLR machinery also linked to autoimmune disease(4,6-9). Loss of this type-I-interferon-inducible protein, which we refer to as '  TLR adaptor interacting with SLC15A4 on the lysosome'  (TASL), abrogated responses to endolysosomal TLR agonists in both primary and transformed human immune cells. Deletion of SLC15A4 or TASL specifically impaired the activation of the IRF pathway without affecting NF-kappa B and MAPK signalling, which indicates that ligand recognition and TLR engagement in the endolysosome occurred normally. Extensive mutagenesis of TASL demonstrated that its localization and function relies on the interaction with SLC15A4. TASL contains a conserved pLxIS motif (in which p denotes a hydrophilic residue and x denotes any residue) that mediates the recruitment and activation of IRF5. This finding shows that TASL is an innate immune adaptor for TLR7, TLR8 and TLR9 signalling, revealing a clear mechanistic analogy with the IRF3 adaptors STING, MAVS and TRIF10,11. The identification of TASL as the component that links endolysosomal TLRs to the IRF5 transcription factor via SLC15A4 provides a mechanistic explanation for the involvement of these proteins in systemic lupus erythematosus(12-14).


  
The architecture of the Gram-positive bacterial cell wall 期刊论文
NATURE, 2020, 582 (7811) : 294-+
作者:  Farquharson, Jamie I.;  Amelung, Falk
收藏  |  浏览/下载:41/0  |  提交时间:2020/07/03

The primary structural component of the bacterial cell wall is peptidoglycan, which is essential for viability and the synthesis of which is the target for crucial antibiotics(1,2). Peptidoglycan is a single macromolecule made of glycan chains crosslinked by peptide side branches that surrounds the cell, acting as a constraint to internal turgor(1,3). In Gram-positive bacteria, peptidoglycan is tens of nanometres thick, generally portrayed as a homogeneous structure that provides mechanical strength(4-6). Here we applied atomic force microscopy(7-12) to interrogate the morphologically distinct Staphylococcus aureus and Bacillus subtilis species, using live cells and purified peptidoglycan. The mature surface of live cells is characterized by a landscape of large (up to 60 nm in diameter), deep (up to 23 nm) pores constituting a disordered gel of peptidoglycan. The inner peptidoglycan surface, consisting of more nascent material, is much denser, with glycan strand spacing typically less than 7 nm. The inner surface architecture is location dependent  the cylinder of B. subtilis has dense circumferential orientation, while in S. aureus and division septa for both species, peptidoglycan is dense but randomly oriented. Revealing the molecular architecture of the cell envelope frames our understanding of its mechanical properties and role as the environmental interface(13,14), providing information complementary to traditional structural biology approaches.


Using high-resolution atomic force microscopy of live cells, the authors present an updated view of the cell walls of both Staphylococcus aureus and Bacillus subtilis.


  
A conserved dendritic-cell regulatory program limits antitumour immunity 期刊论文
NATURE, 2020, 580 (7802) : 257-+
作者:  Perry, Rachel J.;  Zhang, Dongyan;  Guerra, Mateus T.;  Brill, Allison L.;  Goedeke, Leigh;  Nasiri, Ali R.;  Rabin-Court, Aviva;  Wang, Yongliang;  Peng, Liang;  Dufour, Sylvie;  Zhang, Ye;  Zhang, Xian-Man;  Butrico, Gina M.;  Toussaint, Keshia;  Nozaki, Yuichi;  Cline, Gary W.;  Petersen, Kitt Falk;  Nathanson, Michael H.;  Ehrlich, Barbara E.;  Shulman, Gerald I.
收藏  |  浏览/下载:54/0  |  提交时间:2020/07/03

After taking up tumour-associated antigens, dendritic cells in mouse and human tumours upregulate a regulatory gene program that limits dendritic cell immunostimulatory function, and modulating this program can rescue antitumor immunity in mice.


Checkpoint blockade therapies have improved cancer treatment, but such immunotherapy regimens fail in a large subset of patients. Conventional type 1 dendritic cells (DC1s) control the response to checkpoint blockade in preclinical models and are associated with better overall survival in patients with cancer, reflecting the specialized ability of these cells to prime the responses of CD8(+) T cells(1-3). Paradoxically, however, DC1s can be found in tumours that resist checkpoint blockade, suggesting that the functions of these cells may be altered in some lesions. Here, using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, we identify a cluster of dendritic cells (DCs) that we name '  mature DCs enriched in immunoregulatory molecules'  (mregDCs), owing to their coexpression of immunoregulatory genes (Cd274, Pdcd1lg2 and Cd200) and maturation genes (Cd40, Ccr7 and Il12b). We find that the mregDC program is expressed by canonical DC1s and DC2s upon uptake of tumour antigens. We further find that upregulation of the programmed death ligand 1 protein-a key checkpoint molecule-in mregDCs is induced by the receptor tyrosine kinase AXL, while upregulation of interleukin (IL)-12 depends strictly on interferon-gamma and is controlled negatively by IL-4 signalling. Blocking IL-4 enhances IL-12 production by tumour-antigen-bearing mregDC1s, expands the pool of tumour-infiltrating effector T cells and reduces tumour burden. We have therefore uncovered a regulatory module associated with tumour-antigen uptake that reduces DC1 functionality in human and mouse cancers.


  
A mycobacterial ABC transporter mediates the uptake of hydrophilic compounds 期刊论文
NATURE, 2020, 580 (7803) : 409-+
作者:  Al-Shayeb, Basem;  Sachdeva, Rohan;  Chen, Lin-Xing;  Ward, Fred;  Munk, Patrick;  Devoto, Audra;  Castelle, Cindy J.;  Olm, Matthew R.;  Bouma-Gregson, Keith;  Amano, Yuki;  He, Christine;  Meheust, Raphael;  Brooks, Brandon;  Thomas, Alex;  Levy, Adi;  Matheus-Carnevali, Paula;  Sun, Christine;  Goltsman, Daniela S. A.;  Borton, Mikayla A.;  Sharrar, Allison;  Jaffe, Alexander L.;  Nelson, Tara C.;  Kantor, Rose;  Keren, Ray;  Lane, Katherine R.;  Farag, Ibrahim F.;  Lei, Shufei;  Finstad, Kari;  Amundson, Ronald;  Anantharaman, Karthik;  Zhou, Jinglie;  Probst, Alexander J.;  Power, Mary E.;  Tringe, Susannah G.;  Li, Wen-Jun;  Wrighton, Kelly;  Harrison, Sue;  Morowitz, Michael;  Relman, David A.;  Doudna, Jennifer A.;  Lehours, Anne-Catherine;  Warren, Lesley;  Cate, Jamie H. D.;  Santini, Joanne M.;  Banfield, Jillian F.
收藏  |  浏览/下载:67/0  |  提交时间:2020/07/03

Mycobacterium tuberculosis (Mtb) is an obligate human pathogen and the causative agent of tuberculosis(1-3). Although Mtb can synthesize vitamin B-12 (cobalamin) de novo, uptake of cobalamin has been linked to pathogenesis of tuberculosis2. Mtb does not encode any characterized cobalamin transporter(4-6)  however, the gene rv1819c was found to be essential for uptake of cobalamin(1). This result is difficult to reconcile with the original annotation of Rv1819c as a protein implicated in the transport of antimicrobial peptides such as bleomycin(7). In addition, uptake of cobalamin seems inconsistent with the amino acid sequence, which suggests that Rv1819c has a bacterial ATP-binding cassette (ABC)-exporter fold1. Here, we present structures of Rv1819c, which reveal that the protein indeed contains the ABC-exporter fold, as well as a large water-filled cavity of about 7,700 angstrom(3), which enables the protein to transport the unrelated hydrophilic compounds bleomycin and cobalamin. On the basis of these structures, we propose that Rv1819c is a multi-solute transporter for hydrophilic molecules, analogous to the multidrug exporters of the ABC transporter family, which pump out structurally diverse hydrophobic compounds from cells(8-11).


  
Influence of Iron, Cobalt, and Vitamin B-12 Supply on Phytoplankton Growth in the Tropical East Pacific During the 2015 El Nino 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2018, 45 (12) : 6150-6159
作者:  Browning, Thomas J.;  Rapp, Insa;  Schlosser, Christian;  Gledhill, Martha;  Achterberg, Eric P.;  Bracher, Astrid;  Le Moigne, Frederic A. C.
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
phytoplankton  iron  cobalt  vitamin B-12  El Nino  Equatorial Pacific  
Two distinct pools of B-12 analogs reveal community interdependencies in the ocean 期刊论文
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2017, 114 (2) : 364-369
作者:  Heal, Katherine R.;  Qin, Wei;  Ribalet, Francois;  Bertagnolli, Anthony D.;  Coyote-Maestas, Willow;  Hmelo, Laura R.;  Moffett, James W.;  Devol, Allan H.;  Armbrust, E. Virginia;  Stahl, David A.;  Ingalls, Anitra E.
收藏  |  浏览/下载:19/0  |  提交时间:2019/11/27
B-12  cobalamin  Thaumarchaeota  pseudocobalamin  Cyanobacteria