Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.

The ubiquitin-signaling pathway utilizes E1 activating, E2 conjugating, and E3 ligase enzymes to sequentially transfer the small modifier protein ubiquitin to a substrate protein. During the last step of this cascade different types of E3 ligases either act as scaffolds to recruit an E2 enzyme and s...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Donald E Spratt, Pascal Mercier, Gary S Shaw
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b4c21ed199646c8936696acdb2cb886
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3b4c21ed199646c8936696acdb2cb886
record_format	dspace
spelling	oai:doaj.org-article:3b4c21ed199646c8936696acdb2cb8862021-11-18T08:59:21ZStructure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.1932-620310.1371/journal.pone.0074047https://doaj.org/article/3b4c21ed199646c8936696acdb2cb8862013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24058416/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The ubiquitin-signaling pathway utilizes E1 activating, E2 conjugating, and E3 ligase enzymes to sequentially transfer the small modifier protein ubiquitin to a substrate protein. During the last step of this cascade different types of E3 ligases either act as scaffolds to recruit an E2 enzyme and substrate (RING), or form an ubiquitin-thioester intermediate prior to transferring ubiquitin to a substrate (HECT). The RING-inBetweenRING-RING (RBR) proteins constitute a unique group of E3 ubiquitin ligases that includes the Human Homologue of Drosophila Ariadne (HHARI). These E3 ligases are proposed to use a hybrid RING/HECT mechanism whereby the enzyme uses facets of both the RING and HECT enzymes to transfer ubiquitin to a substrate. We now present the solution structure of the HHARI RING2 domain, the key portion of this E3 ligase required for the RING/HECT hybrid mechanism. The structure shows the domain possesses two Zn²⁺-binding sites and a single exposed cysteine used for ubiquitin catalysis. A structural comparison of the RING2 domain with the HECT E3 ligase NEDD4 reveals a near mirror image of the cysteine and histidine residues in the catalytic site. Further, a tandem pair of aromatic residues exists near the C-terminus of the HHARI RING2 domain that is conserved in other RBR E3 ligases. One of these aromatic residues is remotely located from the catalytic site that is reminiscent of the location found in HECT E3 enzymes where it is used for ubiquitin catalysis. These observations provide an initial structural rationale for the RING/HECT hybrid mechanism for ubiquitination used by the RBR E3 ligases.Donald E SprattPascal MercierGary S ShawPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e74047 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Donald E Spratt Pascal Mercier Gary S Shaw Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.
description	The ubiquitin-signaling pathway utilizes E1 activating, E2 conjugating, and E3 ligase enzymes to sequentially transfer the small modifier protein ubiquitin to a substrate protein. During the last step of this cascade different types of E3 ligases either act as scaffolds to recruit an E2 enzyme and substrate (RING), or form an ubiquitin-thioester intermediate prior to transferring ubiquitin to a substrate (HECT). The RING-inBetweenRING-RING (RBR) proteins constitute a unique group of E3 ubiquitin ligases that includes the Human Homologue of Drosophila Ariadne (HHARI). These E3 ligases are proposed to use a hybrid RING/HECT mechanism whereby the enzyme uses facets of both the RING and HECT enzymes to transfer ubiquitin to a substrate. We now present the solution structure of the HHARI RING2 domain, the key portion of this E3 ligase required for the RING/HECT hybrid mechanism. The structure shows the domain possesses two Zn²⁺-binding sites and a single exposed cysteine used for ubiquitin catalysis. A structural comparison of the RING2 domain with the HECT E3 ligase NEDD4 reveals a near mirror image of the cysteine and histidine residues in the catalytic site. Further, a tandem pair of aromatic residues exists near the C-terminus of the HHARI RING2 domain that is conserved in other RBR E3 ligases. One of these aromatic residues is remotely located from the catalytic site that is reminiscent of the location found in HECT E3 enzymes where it is used for ubiquitin catalysis. These observations provide an initial structural rationale for the RING/HECT hybrid mechanism for ubiquitination used by the RBR E3 ligases.
format	article
author	Donald E Spratt Pascal Mercier Gary S Shaw
author_facet	Donald E Spratt Pascal Mercier Gary S Shaw
author_sort	Donald E Spratt
title	Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.
title_short	Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.
title_full	Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.
title_fullStr	Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.
title_full_unstemmed	Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.
title_sort	structure of the hhari catalytic domain shows glimpses of a hect e3 ligase.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/3b4c21ed199646c8936696acdb2cb886
work_keys_str_mv	AT donaldespratt structureofthehharicatalyticdomainshowsglimpsesofahecte3ligase AT pascalmercier structureofthehharicatalyticdomainshowsglimpsesofahecte3ligase AT garysshaw structureofthehharicatalyticdomainshowsglimpsesofahecte3ligase
_version_	1718421075508854784

Structure of the HHARI catalytic domain shows glimpses of a HECT E3 ligase.

Ejemplares similares