ESCRT kompleksi ja postinfektionaalinen antivirusterapiatutkimus - Aihe pohdintaan.

Tässä kun aloin katsoa  toisia E3-ligaaseja TRIM-perheen jälkeen ja tulin HECT- kaltaisiin E3.-ligaaseihin, huomaan että  on otettava ESCRT-kompleksin rakenne lukuaiheeksi, sillä   HECT-kaltaiset ubikitiiniligaasit vaikuttavat  tässä lokalisatiossa.
ESCRT tarkoittaa  Cellular Endoromal Sorting Complex Required for Transport Mechanism.
Monilla viruksilla on l-domaanissaan motiivi joka tunnistaa niitä ESCRT proteiineja ja niihin assosioituneita proteiineja ja jopa rekrytoi ne suoritaakseen virionin  koostamisen ja virionien ulossilmukoimisen.
Tästä tieteestä asetan   linkin (1)  vuodlta 2014. Siinä on etsitty  pieniä  molekyylejä, joka voisi estää viruksen  rekrytoivan motiivin ja  solun  ESCRT- proteiinien välisen yhteyden. Seulottu  70 000 molekyyliä jne mielenkiintoista raporttia.Virusten L-domeenin  motiivit lueteltu, ne jotka rekrytöivät Nedd4 ja Tsg101
 Sitaatti:
One of these L-domain motifs, termed the PTAP motif (for example, from HIV-1), interacts with the TSG101 protein that becomes recruited as part of the ESCRT complexes. Another of these L-domain motifs, termed PPPY motif (also referred to as the “PY motif” or the “PY L-domain motif;” for example, from ASLV), interacts with the Nedd4 family of proteins that is also recruited by ESCRT-associated proteins. While it is often the case, that certain viruses have a viral protein might encode both types of L-domains, typically only one predominates in the viral budding process through interactions with ESCRT machinery. The Applicants have devised novel, robust screening methods to identify compounds that interfere with the interaction between viral L-domains that include the PPPY motif or PTAP motif and ESCRT component, TSG101 or ESCRT-linked component, Nedd4 family proteins. These screening methods enable one to rapidly identify compounds that inhibit the interactions of both Nedd4 and TSG101 with the viral L-domain motifs, thereby providing a high-throughput strategy to obtain candidate lead compounds having utility as novel antiviral agents for inhibiting virus budding and release from infected cells.

(1)  https://patents.google.com/patent/US20140179637A1/en

Kun silmäilee raporttia, siin mainitaan usein  ESCRT- kompleksi. Siitä haluaa tietöä enemmän.
 Linkki (2)
 http://www.biochemsoctrans.org/content/45/3/613
Review Article , Growing functions of the ESCRT machinery in cell biology and viral replication.

Edward J. Scourfield, Juan Martin-Serrano

Biochemical Society Transactions Jun 15, 2017, 45 (3) 613-634; DOI: 10.1042/BST20160479

Abstract

The vast expansion in recent years of the cellular processes promoted by the endosomal sorting complex required for transport (ESCRT) machinery has reinforced its identity as a modular system that uses multiple adaptors to recruit the core membrane remodelling activity at different intracellular sites and facilitate membrane scission. Functional connections to processes such as the aurora B-dependent abscission checkpoint also highlight the importance of the spatiotemporal regulation of the ESCRT machinery.

 Here, we summarise the role of ESCRTs in viral budding, and what we have learned about the ESCRT pathway from studying this process. These advances are discussed in the context of areas of cell biology that have been transformed by research in the ESCRT field, including cytokinetic abscission, nuclear envelope resealing and plasma membrane repair.

Mitä  termejä tähän artikkelin alueeseen kuuluu?  Sitaatista  selviää- ja niitä voi pitää hakusanana.   Joukosta löytyy HECT- kaltaiset E3 ubikitiiniligaasit . 

"Abbreviations

ALG-2, apoptosis-linked gene-2; Apoptoosiin linkkiytynyt geeni 2

ALIX, ALG-2-interacting protein X;  ALG-2:n kannsa interaktion tekevä proteiini X

ANCHR, Abscission/NoCut Checkpoint Regulator; 

ARMM, ARRDC1-mediated microvesicle;

ARRDC1, arrestin domain containing 1; Arrestiinidomaanin sisältävä proteiini1

ART, arrestin-related trafficking;  Arerstiiniin assosioituva kuljetus

CDK1, cyclin-dependent kinase 1; Sykliinistä riippuva kinaasi 1

CEP55, centrosomal protein of 55 kDa; Sentrosomaalinen proteiini 55kDa

CHMP, charged multivesicular body protein;

CPC, chromosomal passenger complex;

CYK-4, cytokeratin-4;

DEEM, deep-etch electron microscopy;

EAP20, ELL-associated protein of 20 kDa;

EAP45, ELL-associated protein of 45 kDa;

EIAV, equine infectious anaemia virus;

ER, endoplasmic reticulum;

ESCRT, endosomal sorting complex required for transport;

HECT, homologous to the E6-AP carboxyl terminus;

hIST1, human Increased sodium tolerance 1;

HIV, human immunodeficiency virus;

HSV-1, herpes simplex virus-1;

ILV, intralumenal vesicle;

INM, inner nuclear membrane;

LIP5, LYST-interacting protein 5;

MHC, major histocompatibility complex;

MIM, MIT domain-interacting motif;

MIT, microtubule-interacting and trafficking;

MITD1, MIT domain containing 1;

MKLP1, mitotic kinesin-like protein 1;

MLV, murine leukaemia virus;

MVB, multivesicular body;

NE,nuclear envelope;

NEDD4, neural precursor cell expressed developmentally down-regulated protein 4; (HECT like)

NPC, nuclear pore complex;

Nup,nucleoporin;

PLK-1,Polo-like kinase 1;

PM,plasma membrane;

RSV,Rous sarcoma virus;

SINC,storage of improperly assembled NPCs;

Snf7, sucrose nonfermenting protein 7;

TCR,T-cell receptor;

TIRF, total internal reflection fluorescence microscopy;

Tsg101, tumour susceptibility gene 101;

UEV, ubiquitin enzyme variant;

UFD1, ubiquitin fusion degradation protein 1;

ULK3, Unc-51-like kinase 3;

VPS, vacuole protein sorting;

WWP1, WW domain containing E3 ubiquitin protein ligase 1; (HECT-like)

WWP2, WW domain containing E3 ubiquitin protein ligase 2; (HECT- like) "