The Habc domain of syntaxin 3 is a ubiquitin binding domain

Abstract Syntaxins are a family of membrane-anchored SNARE proteins that are essential components required for membrane fusion in eukaryotic intracellular membrane trafficking pathways. Syntaxins contain an N-terminal regulatory domain, termed the Habc domain that is not highly conserved at the prim...

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Autores principales:	Adrian J. Giovannone, Elena Reales, Pallavi Bhattaram, Sirpi Nackeeran, Adam B. Monahan, Rashid Syed, Thomas Weimbs
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/312ac1bd715e454dbbec8c5acdc7cf54
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spelling	oai:doaj.org-article:312ac1bd715e454dbbec8c5acdc7cf542021-12-02T12:33:53ZThe Habc domain of syntaxin 3 is a ubiquitin binding domain10.1038/s41598-020-78412-02045-2322https://doaj.org/article/312ac1bd715e454dbbec8c5acdc7cf542020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78412-0https://doaj.org/toc/2045-2322Abstract Syntaxins are a family of membrane-anchored SNARE proteins that are essential components required for membrane fusion in eukaryotic intracellular membrane trafficking pathways. Syntaxins contain an N-terminal regulatory domain, termed the Habc domain that is not highly conserved at the primary sequence level but folds into a three-helix bundle that is structurally conserved among family members. The syntaxin Habc domain has previously been found to be structurally very similar to the GAT domain present in GGA family members and related proteins that are otherwise completely unrelated to syntaxins. Because the GAT domain has been found to be a ubiquitin binding domain we hypothesized that the Habc domain of syntaxins may also bind to ubiquitin. Here, we report that the Habc domain of syntaxin 3 (Stx3) indeed binds to monomeric ubiquitin with low affinity. This domain binds efficiently to K63-linked poly-ubiquitin chains within a narrow range of chain lengths but not to K48-linked poly-ubiquitin chains. Other syntaxin family members also bind to K63-linked poly-ubiquitin chains but with different chain length specificities. Molecular modeling suggests that residues of the GGA3-GAT domain known to be important for ionic and hydrophobic interactions with ubiquitin may have equivalent, conserved residues within the Habc domain of Stx3. We conclude that the syntaxin Habc domain and the GAT domain are both structurally and functionally related, and likely share a common ancestry despite sequence divergence. Binding of Ubiquitin to the Habc domain may regulate the function of syntaxins in membrane fusion or may suggest additional functions of this protein family.Adrian J. GiovannoneElena RealesPallavi BhattaramSirpi NackeeranAdam B. MonahanRashid SyedThomas WeimbsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-10 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adrian J. Giovannone Elena Reales Pallavi Bhattaram Sirpi Nackeeran Adam B. Monahan Rashid Syed Thomas Weimbs The Habc domain of syntaxin 3 is a ubiquitin binding domain
description	Abstract Syntaxins are a family of membrane-anchored SNARE proteins that are essential components required for membrane fusion in eukaryotic intracellular membrane trafficking pathways. Syntaxins contain an N-terminal regulatory domain, termed the Habc domain that is not highly conserved at the primary sequence level but folds into a three-helix bundle that is structurally conserved among family members. The syntaxin Habc domain has previously been found to be structurally very similar to the GAT domain present in GGA family members and related proteins that are otherwise completely unrelated to syntaxins. Because the GAT domain has been found to be a ubiquitin binding domain we hypothesized that the Habc domain of syntaxins may also bind to ubiquitin. Here, we report that the Habc domain of syntaxin 3 (Stx3) indeed binds to monomeric ubiquitin with low affinity. This domain binds efficiently to K63-linked poly-ubiquitin chains within a narrow range of chain lengths but not to K48-linked poly-ubiquitin chains. Other syntaxin family members also bind to K63-linked poly-ubiquitin chains but with different chain length specificities. Molecular modeling suggests that residues of the GGA3-GAT domain known to be important for ionic and hydrophobic interactions with ubiquitin may have equivalent, conserved residues within the Habc domain of Stx3. We conclude that the syntaxin Habc domain and the GAT domain are both structurally and functionally related, and likely share a common ancestry despite sequence divergence. Binding of Ubiquitin to the Habc domain may regulate the function of syntaxins in membrane fusion or may suggest additional functions of this protein family.
format	article
author	Adrian J. Giovannone Elena Reales Pallavi Bhattaram Sirpi Nackeeran Adam B. Monahan Rashid Syed Thomas Weimbs
author_facet	Adrian J. Giovannone Elena Reales Pallavi Bhattaram Sirpi Nackeeran Adam B. Monahan Rashid Syed Thomas Weimbs
author_sort	Adrian J. Giovannone
title	The Habc domain of syntaxin 3 is a ubiquitin binding domain
title_short	The Habc domain of syntaxin 3 is a ubiquitin binding domain
title_full	The Habc domain of syntaxin 3 is a ubiquitin binding domain
title_fullStr	The Habc domain of syntaxin 3 is a ubiquitin binding domain
title_full_unstemmed	The Habc domain of syntaxin 3 is a ubiquitin binding domain
title_sort	habc domain of syntaxin 3 is a ubiquitin binding domain
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/312ac1bd715e454dbbec8c5acdc7cf54
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The Habc domain of syntaxin 3 is a ubiquitin binding domain

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