RT Journal Article
T1 The Habc domain of syntaxin 3 is a ubiquitin binding domain.
A1 Giovannone, Adrian J
A1 Reales, Elena
A1 Bhattaram, Pallavi
A1 Nackeeran, Sirpi
A1 Monahan, Adam B
A1 Syed, Rashid
A1 Weimbs, Thomas
K1 Protein binding
K1 Protein conformation
K1 Qa-SNARE proteins
K1 SNARE proteins
K1 Surface plasmon resonance
AB 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.
PB Nature Publishing Group
YR 2020
FD 2020-11-24
LK http://hdl.handle.net/10668/16749
UL http://hdl.handle.net/10668/16749
LA en
NO Giovannone AJ, Reales E, Bhattaram P, Nackeeran S, Monahan AB, Syed R, et al. The Habc domain of syntaxin 3 is a ubiquitin binding domain. Sci Rep. 2020 Dec 7;10(1):21350
NO Tis work was supported by Grants from the NIH (DK095248, GM66785), and the California Cancer Research Coordinating Committee to T.W., and a Postdoctoral Fellowship from the Spanish Ministry of Education andScience to E.R
DS RISalud
RD Apr 9, 2025