PI fosfolipidiaineenvaihdunta Sars-Cov-1 koronavirusten infektiossa , PI4Kbeta tuottaa PI-4P fosfolipidiä, Fosfatidyyli.4-fosfaattia, (Ptd4P)

 DOI: 10.1074/jbc.M111.312561  Tietoa vuodelta 2012

 Tämä tutkimus on Sars-Cov-1 viruksesta. Tämä  sars-Cov-2 on  tehnyt olennaisen muutoksen juuri tuohon kohtaan  , johon mahdollisesti on  voitu kehittää jokin  inhibiittori.  Koetan   ottaa selvää löytyykö  nykyisestä pandemisesta jotakin  vastaava  akilleenkantapääkohtaa. Tässä ei tarkemmin näytetä tai kerrota mekanismia  sars-1 viruksessa.  (Aichi virus mainitaan).

 2012 Mar 9;287(11):8457-67.

doi: 10.1074/jbc.M111.312561. Epub 2012 Jan 17.

Phosphatidylinositol 4-kinase IIIβ is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry

Ning Yang  ¹ , Ping Ma, Jianshe Lang, Yanli Zhang, Jiejie Deng, Xiangwu Ju, Gongyi Zhang, Chengyu Jiang

• PMCID: PMC3318727
• DOI: 10.1074/jbc.M111.312561

Free PMC article

Abstract

Phosphatidylinositol kinases (PI kinases) play an important role in the life cycle of several viruses after infection. Using gene knockdown technology, we demonstrate that phosphatidylinositol 4-kinase IIIβ (PI4KB) is required for cellular entry by pseudoviruses bearing the severe acute respiratory syndrome-coronavirus (SARS-CoV) spike protein and that the cell entry mediated by SARS-CoV spike protein is strongly inhibited by knockdown of PI4KB. Consistent with this observation, pharmacological inhibitors of PI4KB blocked entry of SARS pseudovirions. Further research suggested that PI4P plays an essential role in SARS-CoV spike-mediated entry, which is regulated by the PI4P lipid microenvironment. We further demonstrate that PI4KB does not affect virus entry at the SARS-CoV S-ACE2 binding interface or at the stage of virus internalization but rather at or before virus fusion. Taken together, these results indicate a new function for PI4KB and suggest a new drug target for preventing SARS-CoV infection.

Katson Gene Cards tiedon:

Entrez Gene Summary for PI4KB Gene

• Enables 1-phosphatidylinositol 4-kinase activity and 14-3-3 protein binding activity. Predicted to be involved in phosphatidylinositol phosphate biosynthetic process and phosphatidylinositol-mediated signaling. Located in Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

GeneCards Summary for PI4KB Gene

PI4KB (Phosphatidylinositol 4-Kinase Beta) is a Protein Coding gene. Diseases associated with PI4KB include Nonparalytic Poliomyelitis and Poliomyelitis. Among its related pathways are Metabolism and PI Metabolism. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and 1-phosphatidylinositol 4-kinase activity. An important paralog of this gene is PI4KA.

UniProtKB/Swiss-Prot Summary for PI4KB Gene

Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking (By similarity). ( PI4KB_HUMAN,Q9UBF8 )

(Microbial infection) Plays an essential role in Aichi virus RNA replication (PubMed:22124328, 27989622, 22258260). Recruited by ACBD3 at the viral replication sites (PubMed:22124328, 27989622). ( PI4KB_HUMAN,Q9UBF8 )

(Microbial infection) Required for cellular spike-mediated entry of human coronavirus SARS-CoV. ( PI4KB_HUMAN,Q9UBF8 )

Gene Wiki entry for PI4KB Gene

Aliases for PI4KB Gene

• GeneCards Symbol: PI4KB ²
• Phosphatidylinositol 4-Kinase Beta ^{2 3 4 5}
• PI4K-BETA ^{2 3 5}
• PIK4CB ^{3 4 5}
• Phosphatidylinositol 4-Kinase, Catalytic, Beta ^{2 3}
• PtdIns 4-Kinase Beta ^{3 4}
• EC 2.7.1.67 ^{4 48}
• PI4KIII ^{3 4}
• Pi4K92 ^{2 5}

• PI4K92 ^{3 4}
• NPIK ^{3 4}
• Phosphatidylinositol 4-Kinase, Wortmannin-Sensitive ³
• Type III Phosphatidylinositol 4-Kinase Beta ³
• PI4KIIIBETA ³
• PI4K-Beta ⁴
• PI4KBETA ³
• PI4Kbeta ⁴
• EC 2.7.1 ⁴⁸

 1q21.3

Protein Symbol: Q9UBF8-PI4KB_HUMAN

Recommended name: Phosphatidylinositol 4-kinase beta

Size: 816 amino acids

Molecular mass: 91379 Da

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;

Cofactor: Name=Mn(2+); Xref=ChEBI:CHEBI:29035;

Protein existence level:

PE1

Quaternary structure:

• Interacts with ARF1 and ARF3 in the Golgi complex, but not with ARF4, ARF5 or ARF6 (PubMed:17555535).
  Interacts with NCS1/FREQ in a calcium-independent manner.
  Interacts with CALN1/CABP8 and CALN2/CABP7; in a calcium-dependent manner; this interaction competes with NCS1/FREQ binding (By similarity).
  Interacts with ACBD3 (PubMed:23572552, 27009356, 27989622, 22124328, 22258260).
  Interacts with ARMH3, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN (PubMed:23572552).
  Interacts with GGA2 (via VHS domain); the interaction is important for PI4KB location at the Golgi apparatus membrane (PubMed:28289207).
  Interacts with ATG9A (PubMed:30917996).
• (Microbial infection) Interacts with Aichi virus protein 3A.
  Part of a complex Aichi virus protein 3A/ACBD3/PI4KB that allows the synthesis of PI4P at the viral RNA replication sites.

 

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