PDBsum entry 2al3

Endocytosis/exocytosis

PDB id: 2al3

Contents

Protein chain

76 a.a. *

* Residue conservation analysis

PDB id:

2al3

Name:

Endocytosis/exocytosis

Title:

Solution structure and backbone dynamics of an n-terminal ubiquitin- like domain in the glut4-tethering protein, tug

Structure:

Tug long isoform. Chain: a. Fragment: n-terminal ubiquitin-like domain (residues 1-90). Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: tug. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

NMR struc:

20 models

Authors:

M.C.Tettamanzi,C.Yu,J.S.Bogan,M.E.Hodsdon

Key ref:

M.C.Tettamanzi et al. (2006). Solution structure and backbone dynamics of an N-terminal ubiquitin-like domain in the GLUT4-regulating protein, TUG. Protein Sci, 15, 498-508. PubMed id: 16501224 DOI: 10.1110/ps.051901806

Date:

04-Aug-05 Release date: 21-Mar-06

Protein chain

Q8VBT9  (ASPC1_MOUSE) -  Tether containing UBX domain for GLUT4 from Mus musculus

Seq: 550 a.a.

Struc: 76 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1110/ps.051901806

Protein Sci 15:498-508 (2006)

PubMed id: 16501224

Solution structure and backbone dynamics of an N-terminal ubiquitin-like domain in the GLUT4-regulating protein, TUG.

M.C.Tettamanzi, C.Yu, J.S.Bogan, M.E.Hodsdon.

ABSTRACT

The GLUT4-regulating protein, TUG, functions to retain GLUT4-containing membrane vesicles intracellularly and, in response to insulin stimulation, releases these vesicles to the cellular exocytic machinery for translocation to the plasma membrane. As part of our on going effort to describe the molecular basis for TUG function, we have determined the tertiary structure and characterized the backbone dynamics for an N-terminal ubiquitin-like domain (TUG-UBL1) using NMR spectroscopy. A well-ordered conformation is observed for residues 10-83 of full-length TUG, and confirms a beta-grasp or ubiquitin-like topology. Although not required for in vitro association with GLUT4, the functional role of the TUG-UBL1 domain has not yet been described. We undertook a limited literature review of similar N-terminal UBL domains and noted that a majority participate in protein-protein interactions, generally functioning as adaptor modules to physically associate the over all activity of the protein with a specific cellular process, such as the ubiquitin-proteasome pathway. In consistent fashion, TUG-UBL1 is not expected to participate in a covalent protein modification reaction as it lacks the characteristic C-terminal diglycine ("GG") motif required for conjugation to an acceptor lysine, and also lacks the three most common acceptor lysine residues involved in polyubiquitination. Additionally, analysis of the TUG-UBL1 molecular surface reveals a lack of conservation of the "Ile-44 hydrophobic face" typically involved in ubiquitin recognition. Instead, we speculate on the possible significance of a concentrated area of negative electrostatic potential with increased backbone mobility, both of which are features suggestive of a potential protein-protein interaction site.

Selected figure(s)

Figure 2.
The 2D ^1H-^15N HSQC NMR spectrum of TUG --UBL1. Backbone amide correlations are labeled for all nonprolyl residues from A2 to N90, along with the side-chain [var epsilon]2 amide for W65.

Figure 3.
The tertiary structure of TUG --UBL1 as determined by NMR spectroscopy. (A) Superposed C[alpha] traces for the ensemble of 20 NMR structures, rainbow-colored from red at the N terminus to blue at the C terminus, prepared using MOLSCRIPT (Kraulis 1991). (B) Backbone ribbon diagram for a representative member of the NMR ensemble demonstrating the [beta]-grasp topology conserved within this protein family, prepared using MOLMOL (Koradi et al. 1996).

The above figures are reprinted from an Open Access publication published by the Protein Society: Protein Sci (2006, 15, 498-508) copyright 2006.

Figures were selected by an automated process.