Electron microscopy studies of Type III CRISPR machines in Sulfolobus solfataricus

2013 ◽  
Vol 41 (6) ◽  
pp. 1427-1430 ◽  
Author(s):  
Giuseppe Cannone ◽  
Mariam Webber-Birungi ◽  
Laura Spagnolo
Keyword(s):  
Electron Microscopy ◽  
Immune System ◽  
Unit Length ◽  
Sulfolobus Solfataricus ◽  
Adaptive Immune System ◽  
Particle Analysis ◽  
Single Particle Analysis ◽  
Type Iii Effector ◽  
Type Iii ◽  
Adaptive Immune

The CRISPR (clustered regularly interspaced short palindromic repeats) system is an adaptive immune system that targets viruses and other mobile genetic elements in bacteria and archaea. Cells store information of past infections in their genome in repeat–spacer arrays. After transcription, these arrays are processed into unit-length crRNA (CRISPR RNA) that is loaded into effector complexes encoded by Cas (CRISPR-associated) genes. CRISPR–Cas complexes target invading nucleic acid for degradation. CRISPR effector complexes have been classified into three main types (I–III). Type III effector complexes share the Cas10 subunit. In the present paper, we discuss the structures of the two Type III effector complexes from Sulfolobus solfataricus, SsoCSM (subtype III-A) and SsoCMR (subtype III-B), obtained by electron microscopy and single particle analysis. We also compare these structures with Cascade (CRISPR-associated complex for antiviral defence) and with the RecA nucleoprotein.

scholarly journals Structure of a dimeric crenarchaeal Cas6 enzyme with an atypical active site for CRISPR RNA processing

2013 ◽  
Vol 452 (2) ◽  
pp. 223-230 ◽  
Author(s):  
Judith Reeks ◽  
Richard D. Sokolowski ◽  
Shirley Graham ◽  
Huanting Liu ◽  
James H. Naismith ◽  
...  
Keyword(s):  
Rna Processing ◽  
Active Site ◽  
Essential Feature ◽  
Unit Length ◽  
Sulfolobus Solfataricus ◽  
Adaptive Immune System ◽  
Direct Repeats ◽  
Specific Detection ◽  
Adaptive Immune ◽  
Structure And Activity

The competition between viruses and hosts is played out in all branches of life. Many prokaryotes have an adaptive immune system termed ‘CRISPR’ (clustered regularly interspaced short palindromic repeats) which is based on the capture of short pieces of viral DNA. The captured DNA is integrated into the genomic DNA of the organism flanked by direct repeats, transcribed and processed to generate crRNA (CRISPR RNA) that is loaded into a variety of effector complexes. These complexes carry out sequence-specific detection and destruction of invading mobile genetic elements. In the present paper, we report the structure and activity of a Cas6 (CRISPR-associated 6) enzyme (Sso1437) from Sulfolobus solfataricus responsible for the generation of unit-length crRNA species. The crystal structure reveals an unusual dimeric organization that is important for the enzyme's activity. In addition, the active site lacks the canonical catalytic histidine residue that has been viewed as an essential feature of the Cas6 family. Although several residues contribute towards catalysis, none is absolutely essential. Coupled with the very low catalytic rate constants of the Cas6 family and the plasticity of the active site, this suggests that the crRNA recognition and chaperone-like activities of the Cas6 family should be considered as equal to or even more important than their role as traditional enzymes.

Evolution and age characteristics of the innate and adaptive immune system

2016 ◽  
Vol 75 (3) ◽  
pp. 74-84 ◽  
Author(s):  
A.E. Abaturov ◽  
◽  
E.A. Agafonova ◽  
N.I. Abaturova ◽  
V.L. Babich ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Adaptive Immune

scholarly journals Unfolded Protein Corona Surrounding Nanotubes Influence the Innate and Adaptive Immune System

2021 ◽  
Vol 8 (8) ◽  
pp. 2004979
Author(s):  
Jun‐Young Park ◽  
Sung Jean Park ◽  
Jun Young Park ◽  
Sang‐Hyun Kim ◽  
Song Kwon ◽  
...  
Keyword(s):  
Immune System ◽  
Adaptive Immune System ◽  
Protein Corona ◽  
Unfolded Protein ◽  
Adaptive Immune

scholarly journals T Cells Limit Accumulation of Aggregate Pathology Following Intrastriatal Injection of α-Synuclein Fibrils

2021 ◽  
pp. 1-19
Author(s):  
Sonia George ◽  
Trevor Tyson ◽  
Nolwen L. Rey ◽  
Rachael Sheridan ◽  
Wouter Peelaerts ◽  
...  
Keyword(s):  
T Cells ◽  
Immune System ◽  
B Cells ◽  
Substantia Nigra ◽  
Adaptive Immune System ◽  
Proteinase K ◽  
T And B Cells ◽  
Adaptive Immune ◽  
Immunocompromised Mice ◽  
The Impact

Background: α-Synuclein (α-syn) is the predominant protein in Lewy-body inclusions, which are pathological hallmarks of α- synucleinopathies, such as Parkinson’s disease (PD) and multiple system atrophy (MSA). Other hallmarks include activation of microglia, elevation of pro-inflammatory cytokines, as well as the activation of T and B cells. These immune changes point towards a dysregulation of both the innate and the adaptive immune system. T cells have been shown to recognize epitopes derived from α-syn and altered populations of T cells have been found in PD and MSA patients, providing evidence that these cells can be key to the pathogenesis of the disease. Objective To study the role of the adaptive immune system with respect to α-syn pathology. Methods: We injected human α-syn preformed fibrils (PFFs) into the striatum of immunocompromised mice (NSG) and assessed accumulation of phosphorylated α-syn pathology, proteinase K-resistant α-syn pathology and microgliosis in the striatum, substantia nigra and frontal cortex. We also assessed the impact of adoptive transfer of naïve T and B cells into PFF-injected immunocompromised mice. Results: Compared to wildtype mice, NSG mice had an 8-fold increase in phosphorylated α-syn pathology in the substantia nigra. Reconstituting the T cell population decreased the accumulation of phosphorylated α-syn pathology and resulted in persistent microgliosis in the striatum when compared to non-transplanted mice. Conclusion: Our work provides evidence that T cells play a role in the pathogenesis of experimental α-synucleinopathy.

scholarly journals Programming Native CRISPR Arrays for the Generation of Targeted Immunity

mBio ◽  
2016 ◽  
Vol 7 (3) ◽  
Author(s):  
Alexander P. Hynes ◽  
Simon J. Labrie ◽  
Sylvain Moineau
Keyword(s):  
Immune System ◽  
Nucleic Acid ◽  
Genome Editing ◽  
Dna Sequence ◽  
Adaptive Immune System ◽  
Natural Process ◽  
The Public ◽  
Adaptive Immune ◽  
Public Consciousness ◽  
Industrial Settings

ABSTRACT The adaptive immune system of prokaryotes, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated genes), results in specific cleavage of invading nucleic acid sequences recognized by the cell’s “memory” of past encounters. Here, we exploited the properties of native CRISPR-Cas systems to program the natural “memorization” process, efficiently generating immunity not only to a bacteriophage or plasmid but to any specifically chosen DNA sequence. IMPORTANCE CRISPR-Cas systems have entered the public consciousness as genome editing tools due to their readily programmable nature. In industrial settings, natural CRISPR-Cas immunity is already exploited to generate strains resistant to potentially disruptive viruses. However, the natural process by which bacteria acquire new target specificities (adaptation) is difficult to study and manipulate. The target against which immunity is conferred is selected stochastically. By biasing the immunization process, we offer a means to generate customized immunity, as well as provide a new tool to study adaptation.

scholarly journals Effects of helium and air inhalation on the innate and early adaptive immune system in healthy volunteers ex vivo

2012 ◽  
Vol 10 (1) ◽  
pp. 201 ◽  
Author(s):  
Gezina TML Oei ◽  
Kirsten F Smit ◽  
Djai vd Vondervoort ◽  
Daniel Brevoord ◽  
Arjan Hoogendijk ◽  
...  
Keyword(s):  
Immune System ◽  
Healthy Volunteers ◽  
Ex Vivo ◽  
Adaptive Immune System ◽  
Adaptive Immune
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