Furan cleavage site

Extracted Attributes

• Name

  Furin cleavage site (Note: The provided document uses "Furan cleavage site", but scientific sources confirm "Furin cleavage site" is the correct term for the biological concept.)

• Function

  Essential for the proteolytic activation of certain viral proteins, facilitating viral entry into host cells and enhancing transmissibility and pathogenicity.

• Definition

  A specific amino acid sequence on a protein that is recognized and cleaved by the ubiquitous protease furin.

• Consensus Motif

  R-x-x-R (arginine at P4 and P1), with a preference for a basic residue at P2 (R-x-K/R-R)

• Scientific Field

  Virology, Molecular Biology, Biochemistry

• Associated Protease

  Furin (a serine protease)

• Significance in SARS-CoV-2

  The SARS-CoV-2 spike glycoprotein contains a furin-like cleavage site (SPRRAR|S) at the S1/S2 interface, which is unusual for sarbecoviruses and is thought to make the virus more transmissible.

Timeline

• The spike glycoprotein of the new coronavirus 2019-nCoV (SARS-CoV-2) was identified to contain a furin-like cleavage site, which was absent in coronaviruses of the same clade. (Source: web_search_results)

  2020-04

• The furin cleavage site on the SARS-CoV-2 virus was discussed as enabling its spikes to be cut and "primed" as it moves out of one cell and into another, potentially making the virus more transmissible, in the context of the origin of COVID-19. (Source: web_search_results)

  2021-10-11

• The virus's "Furan cleavage site" (referring to Furin cleavage site) was scrutinized as evidence in the COVID-19 investigation, particularly concerning the lab leak theory and the funding of gain-of-function research at the Wuhan Institute of Virology. (Source: related_documents)

  Undated

Self-healing material

Self-healing materials are artificial or synthetically created substances that have the built-in ability to automatically repair damages to themselves without any external diagnosis of the problem or human intervention. Generally, materials will degrade over time due to fatigue, environmental conditions, or damage incurred during operation. Cracks and other types of damage on a microscopic level have been shown to change thermal, electrical, and acoustical properties of materials, and the propagation of cracks can lead to eventual failure of the material. In general, cracks are hard to detect at an early stage, and manual intervention is required for periodic inspections and repairs. In contrast, self-healing materials counter degradation through the initiation of a repair mechanism that responds to the micro-damage. Some self-healing materials are classed as smart structures, and can adapt to various environmental conditions according to their sensing and actuation properties. Although the most common types of self-healing materials are polymers or elastomers, self-healing covers all classes of materials, including metals, ceramics, and cementitious materials. Healing mechanisms vary from an instrinsic repair of the material to the addition of a repair agent contained in a microscopic vessel. For a material to be strictly defined as autonomously self-healing, it is necessary that the healing process occurs without human intervention. Self-healing polymers may, however, activate in response to an external stimulus (light, temperature change, etc.) to initiate the healing processes. A material that can intrinsically correct damage caused by normal usage could prevent costs incurred by material failure and lower costs of a number of different industrial processes through longer part lifetime, and reduction of inefficiency caused by degradation over time.

Web Search Results

• Analysis of the molecular determinants for furin cleavage of the ...

  protease cleavage-activation site at the S1/S2 interface of S, which meets the consensus motif for cleavage by the ubiquitous protease furin. Based on convention of terminology for protease specificity (Polgár,1989), a furin cleavage site is composed of arginine (R) residues that are required at the core P4 and P1 cleavage residues (R-x-x-R) and a preference for a basic residue at P2 (_i.e._, R-x-K/R-R) (Osman et al., 2022, Henrich et al., 2003). In many coronaviruses, such furin cleavage sites [...] As is common in the embecoviruses, and similar to SARS-CoV-2, the S protein of many MHV strains contains an RXXR sequence within the S protein, suggesting that they contain a functional furin cleavage site. Indeed, it has been known for many years that the S proteins of murine coronaviruses can be cleaved, but early studies showed that this occurs to different extents depending on the virus strain and the cell line used (Frana et al., 1985). Cleavage of the prototype strain MHV-A59 S protein [...] From a structural perspective, a change (e.g., decrease) in the probability of cleavage for different MHV strains is connected to the effect of the resulting differences in the conformation of the active site region of the catalytic complex with furin. Thus, a difference in the sequence of the cleavage site will affect the way furin (or other protease) must present its catalytic site following binding of the S1/S2 loop to initiate cleavage. As a serine protease, furin utilizes a catalytic triad

• Furin - Homo sapiens (Human) | UniProtKB | UniProt

  | | Type | ID | Position(s) | Description | | --- --- --- | | | Site | | 75-76 | Cleavage, second; by autolysis | | | | | | Site | | 107-108 | Cleavage, first; by autolysis | | | | | | Binding site | | 115 | Ca2+ 1 (UniProtKB | ChEBI) | | | | | | Active site | | 153 | Charge relay system | | | | | | Binding site | | 154 | substrate | | | | | | Binding site | | 162 | Ca2+ 1 (UniProtKB | ChEBI) | | | | | | Binding site | | 174 | Ca2+ 2 (UniProtKB | ChEBI) | | | | [...] (Microbial infection) Facilitates human coronaviruses EMC and SARS-CoV-2 infections by proteolytically cleaving the spike protein at the monobasic S1/S2 cleavage site. This cleavage is essential for spike protein-mediated cell-cell fusion and entry into human lung cells. (Microbial infection) Facilitates mumps virus infection by proteolytically cleaving the viral fusion protein F. ### Catalytic activity [...] Note: Shuttles between the trans-Golgi network and the cell surface (PubMed:11799113, PubMed:9412467). Propeptide cleavage is a prerequisite for exit of furin molecules out of the endoplasmic reticulum (ER). A second cleavage within the propeptide occurs in the trans Golgi network (TGN), followed by the release of the propeptide and the activation of furin (PubMed:11799113).

• Furin - Wikipedia

  17. ^ "The origin of COVID-19: Evidence piles up, but the jury's still out". 11 October 2021. The furin cleavage site on the SARS-CoV-2 virus allows its spikes to be cut and "primed" as it moves out of one cell and into another. The site is thought to make the virus more transmissible. [...] 15. ^ Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E (April 2020). "The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade". Antiviral Research. 176 104742. doi "Doi (identifier)"):10.1016/j.antiviral.2020.104742. PMC "PMC (identifier)") 7114094. PMID "PMID (identifier)") 32057769. [...] 9. ^ Lin L, Nemeth E, Goodnough JB, Thapa DR, Gabayan V, Ganz T (2008). "Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site". Blood Cells, Molecules & Diseases. 40 (1): 122–31. doi "Doi (identifier)"):10.1016/j.bcmd.2007.06.023. PMC "PMC (identifier)") 2211380. PMID "PMID (identifier)") 17869549.

• SARS-CoV-2 spike and its adaptable furin cleavage site - The Lancet

  For coronaviruses, furin cleavage sites at the interface of the S1 and S2 domain are not unusual, being found widely in betacoronaviruses in the embeco lineage (which are considered to be of rodent origin) as well as in avian-origin gammacoronaviruses and certain feline and canine alphacoronaviruses (with an unknown origin). Furin cleavage sites are also found in certain bat-origin MERS-like merbecovirises, but not—with the exception of SARS-CoV-2—in the sarbecovirus lineage. The presence of a [...] but generally only at low levels. Furin has a well known role in viral pathogenesis and efficiently cleaves polybasic or multi-basic sites such as those found in influenza virus subtypes H5 and H7. These highly pathogenic avian influenza viruses have therefore served as a model for the role of furin cleavage as a viral virulence factor. Mechanistically, this furin site is created through polymerase slippage during replication and occurs at the interface of the HA1 and HA2 subdomains. Such [...] Much attention has been drawn to the origin of SARS-CoV-2, the causative agent of COVID-19. One notable feature of SARS-CoV-2 is a four-amino acid insert starting with proline (SPRRAR|S) at the junction of the receptor-binding (S1) and fusion (S2) domains of the spike protein. Following the release of the SARS-CoV-2 genome, several groups identified this insert as a potential cleavage site for the protease furin—the insert has also been referred to as a polybasic site and proposed to be part of

• Mechanistic and predictive studies on the oxidation of furans by ...

  2005). Upon analyzing optimized structures derived from transition states and comparing them to the C2 site (LS/HS: C-O bond length: 2.016/1.929 Å, Fe-O bond length: 1.689/1.708 Å), it is observed that the C5 site exhibits a comparatively longer C-O bond (LS/HS: 2.113/1.981 Å) and a relatively shorter Fe-O bond (LS/HS: 1.664/1.701 Å), especially pronounced in the LS state. This observation implies that the C5 site is positioned relatively earlier along the reaction coordinate. [...] for oxidative metabolism of furan compounds (Gill et al., 2014, Ravindranath, 1986, Ravindranath et al., 1984a), we believe that there is regioselectivity in the active metabolism site of CYP450-mediated 2-methylfuran, due to the difference in electron density and the spatial barrier of substituents. [...] The AIPs and CCFs of the 11 furans obtained through DFT calculations are presented in Table 1. The AIPs of these furans range from 7.20 to 9.16 eV, while the CCFs range from 0.16 to 0.34. The selection of the O-addition reaction site is based on the value of f s 0, where higher values indicate lower energy requirements for C-O bond formation, making it easier to form the bond (Gingrich et al., 2022). Further calculations accounting for ZPE corrections were conducted on the reaction sites with