Regulation of Protein-Protein Interactions by the SUMO and Ubiquitin Pathways

Yanku, Yifat; Orian, Amir

doi:10.5772/38100

Cited by 2 publications

(1 citation statement)

References 85 publications

(84 reference statements)

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“…Furthermore, pathogens like bacteria and viruses also possess such sites, which helps them better adapt to their host environment [66]. Some viruses even code for enzymes that help in virus modification [67,68]. In our study, we identified several distinct mutations in the E, M, and S protein of SARS-CoV-2.…”

Section: Discussionmentioning

confidence: 69%

Mutational analysis of structural proteins of SARS-CoV-2

Jakhmola

Indari

Kashyap

et al. 2021

Heliyon

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SARS-CoV-2 transmissibility is higher than that of other human coronaviruses; therefore, it poses a threat to the populated communities. We investigated mutations among envelope (E), membrane (M), and spike (S) proteins from different isolates of SARS-CoV-2 and plausible signaling influenced by mutated virus in a host. We procured updated protein sequences from the NCBI virus database. Mutations were analyzed in the retrieved sequences of the viral proteins through multiple sequence alignment. Additionally, the data was subjected to ScanPROSITE to analyse if the mutations generated a relevant sequence for host signaling. Unique mutations in E, M, and S proteins resulted in modification sites like PKC phosphorylation and N-myristoylation sites. Based on structural analysis, our study revealed that the D614G mutation in the S protein diminished the interaction with T859 and K854 of adjacent chains. Moreover, the S protein of SARS-CoV-2 consists of an Arg-Gly-Asp (RGD) tripeptide sequence, which could potentially interact with various members of integrin family receptors. RGD sequence in S protein might aid in the initial virus attachment. We speculated crucial host pathways which the mutated isolates of SARS-CoV-2 may alter like PKC, Src, and integrin mediated signaling pathways. PKC signaling is known to influence the caveosome/raft pathway which is critical for virus entry. Additionally, the myristoylated proteins might activate NF-κB, a master molecule of inflammation. Thus the mutations may contribute to the disease pathogenesis and distinct lung pathophysiological changes. Further the frequently occurring mutations in the protein can be studied for possible therapeutic interventions.

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Section: Discussionmentioning

confidence: 69%

Mutational analysis of structural proteins of SARS-CoV-2

Jakhmola

Indari

Kashyap

et al. 2021

Heliyon

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ZASP Interacts with the Mechanosensing Protein Ankrd2 and p53 in the Signalling Network of Striated Muscle

et al. 2014

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ZASP is a cytoskeletal PDZ-LIM protein predominantly expressed in striated muscle. It forms multiprotein complexes and plays a pivotal role in the structural integrity of sarcomeres. Mutations in the ZASP protein are associated with myofibrillar myopathy, left ventricular non-compaction and dilated cardiomyopathy. The ablation of its murine homologue Cypher results in neonatal lethality. ZASP has several alternatively spliced isoforms, in this paper we clarify the nomenclature of its human isoforms as well as their dynamics and expression pattern in striated muscle. Interaction is demonstrated between ZASP and two new binding partners both of which have roles in signalling, regulation of gene expression and muscle differentiation; the mechanosensing protein Ankrd2 and the tumour suppressor protein p53. These proteins and ZASP form a triple complex that appears to facilitate poly-SUMOylation of p53. We also show the importance of two of its functional domains, the ZM-motif and the PDZ domain. The PDZ domain can bind directly to both Ankrd2 and p53 indicating that there is no competition between it and p53 for the same binding site on Ankrd2. However there is competition for this binding site between p53 and a region of the ZASP protein lacking the PDZ domain, but containing the ZM-motif. ZASP is negative regulator of p53 in transactivation experiments with the p53-responsive promoters, MDM2 and BAX. Mutations in the ZASP ZM-motif induce modification in protein turnover. In fact, two mutants, A165V and A171T, were not able to bind Ankrd2 and bound only poorly to alpha-actinin2. This is important since the A165V mutation is responsible for zaspopathy, a well characterized autosomal dominant distal myopathy. Although the mechanism by which this mutant causes disease is still unknown, this is the first indication of how a ZASP disease associated mutant protein differs from that of the wild type ZASP protein.

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Regulation of Protein-Protein Interactions by the SUMO and Ubiquitin Pathways

Cited by 2 publications

References 85 publications

Mutational analysis of structural proteins of SARS-CoV-2

Mutational analysis of structural proteins of SARS-CoV-2

ZASP Interacts with the Mechanosensing Protein Ankrd2 and p53 in the Signalling Network of Striated Muscle

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