FYVE- Znf proteiineja on SARS CoV. interaktioproteiinien joukossa.

ZFYVE sinkkisormiproteiinit, joihin SARS2 CoV tekee interaktion: FYCO1 ja PLEKFH2. Mahdollisesti niiden kautta laajempiinkin komplekseihin.

SARS CoV nsp13 helikaasi  tekee interaktion FYCO1 proteiiniin (ZFYVE7), (3p21.31). 

FYCO1. https://www.genecards.org/cgi-bin/carddisp.pl?gene=FYCO1&keywords=FYCO1

• This gene encodes a protein that contains a RUN domain, FYVE-type zinc finger domain and Golgi dynamics (GOLD) domain. The encoded protein plays a role in microtubule plus end-directed transport of autophagic vesicles through interactions with the small GTPase Rab7, phosphatidylinositol-3-phosphate (PI3P) and the autophagosome marker LC3. Mutations in this gene are a cause of autosomal recessive congenital cataract-2 (CATC2). [provided by RefSeq, Dec 2011]
  FYCO1 (FYVE And Coiled-Coil Domain Autophagy Adaptor 1) is a Protein Coding gene. Diseases associated with FYCO1 include Cataract 18 and Cataract 44. Gene Ontology (GO) annotations related to this gene include nucleotide binding. An important paralog of this gene is RUFY4.
  FYVE domain found in FYVE and coiled-coil domain-containing protein 1 (FYCO1) and similar proteins
  FYCO1, also termed zinc finger FYVE domain-containing protein 7, is a phosphatidylinositol 3-phosphate (PtdIns3P or PI3P)-binding protein that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport. It acts as an effector of GTP-bound Rab7, a GTPase that recruits FYCO1 to autophagosomes and has been implicated in autophagosome-lysosomal fusion. FYCO1 also interacts with two microtubule motor proteins, kinesin (KIF) 5B and KIF23, and thus functions as a platform for assembly of vesicle fusion and trafficking factors. FYCO1 contains an N-terminal alpha-helical RUN domain followed by a long central coiled-coil region, a FYVE domain and a GOLD (Golgi dynamics) domain in C-terminus.putative Zn binding site [ion binding site], 8 residue positions
  Conserved feature residue pattern:C C C C C C C C

 https://www.researchgate.net/figure/Graphical-representation-of-diverse-domain-fold-and-metal-coordination-within-multiple-ZF_fig4_324280754

SARS COV  ORF7 tekee interaktion PLEKHF2 proteiiniin (ZFYVE18)(8q22.1) 

 

PLEKHF2 (Pleckstrin Homology And FYVE Domain Containing 2) is a Protein Coding gene. An important paralog of this gene is PLEKHF1.May play a role in early endosome fusion upstream of RAB5, hence regulating receptor trafficking and fluid-phase transport. Enhances cellular sensitivity to TNF-induced apoptosis (PubMed:18288467).PKHF2_HUMAN,Q9H8W4  Size:249 amino acidsMolecular mass: 27798 Da    (Quaternary structure: May interact with EEA1 (ZFYVE2, 2q22) https://www.genecards.org/cgi-bin/carddisp.pl?gene=EEA1&keywords=EEA1  Among its related pathways are Innate Immune System and Phagosome.  Quaternary structure: Homodimer. Binds STX6. Binds RAB5A, RAB5B, RAB5C and RAB22A that have been activated by GTP-binding. Interacts with RAB31. Interacts with ERBB2. Interacts with SAMD9 AND SAMD9L (PubMed:24029230). May interact with PLEKHF2.. Miscellaneous Antibodies against EEA1 are found in sera from patients with subacute cutaneous lupus erythematosus and other autoimmune diseases.

FYVE domeenin merkityksestä: 

FYVE domains bind Phosphatidylinositol 3-phosphate (PI3P) , in a way dependent on its metal ion coordination and basic amino acids. 

The FYVE domain inserts into cell membranes in a pH-dependent manner. 

The FYVE domain has been connected to vacuolar protein sorting and endosome function.

https://www.ncbi.nlm.nih.gov/pubmed/25985087

 (Suom.) FYVEsinkkisormidomeeni sinkkiproteiinissa linkitsee erityisesti mRNA-kuljetuksen endosomaaliseen liikennöintijärjestelmään. Lähetti RNA:lla on lähiyhteys kalvokuljetukseen. Hyvänä esimerkkinä on mRNA:n ja endosomiin assosioituneiden ribosomien mikrotubuluksista riippuva kuljetus. Tämä koordinoitunut prosessi on ratkaiseva korrektissa septiinifilamentaatiossa ja polarisoituneiden solujen tehokkaassa kasvussa, esim sienirihmastossa. Vaikka tiedetäänkin yksityiskohtia avainasemassa olevista RNA:ta sitovista proteiineista ja molekulaarisista moottoripoteiineista, on kuitenkin epäselvä, miten mRNA on liittynyt kalvoihin kuljetuksen aikana. Tutkijat ovat tunnistaneet uuden tekijän, jossa on FYVE sinkkisormidomeeni, jolla tapahtuu interaktio endosomilipideihin sekä uuden PAM2-kaltaisen domeenin, jota tarvitaan avain asemassa olevaan RNA.ta sitovan proteiiniN MLLE- domeenin kanssa. Johdonmukaisesti FYVE-domeeni proteenin menetys johtaa mRNA:- , ribosomi- ja septiinikuljetuksessa spesifisiin puutteisiin, vaikka endosomein ja niiden liikkeen yleisfunktiot eivät vaikutu. Tämä on ensimmäinen havaittu endosomaalinen komponentti, joka on mRNP-kuljetukselle spesifinen , mistä selviää, että on olemassa eräs uusi mekanismi, jolla mRNA liittyy endosomeihin.

Sinkkisormidomeeni voidaan  kaavamaisesti   ilmaista : CCCCCCCC

tai selkeämmin C-x-C-x-C-x-C-xxx-C-x-C-x-C-x-C, mistä näkee että  ensimmäiset  neljä cysteiiniä ovat  ryhmittyneet  sinkin ympärille  aika lähekkäin, sitten on enemmn aminohappoväliä ja toinen ryväs neljä cysteiiniä (ja niihin koordinoitunut Zn). Maininta FYVE,ilmaisee  mikä  sinkkikooridaatiomalli on kyseessä  ( tässä cross-brace topologia)

Elife. 2015 May 18;4. doi: 10.7554/eLife.06041.

A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking.

Pohlmann T¹, Baumann S¹, Haag C¹, Albrecht M², Feldbrügge M¹.Abstract

An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein. Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement. Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes.

KEYWORDS: FYVE; PAM2; RRM; Ustilago maydis; cell biology; endosome; infectious disease; mRNA transport; microbiology