PDBsum entry 1br0

Membrane protein

PDB id: 1br0

Contents

Protein chain

120 a.a. *

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Three-Dimensional structure of an evolutionarily conserved n-Terminal domain of syntaxin 1a.

Authors

I.Fernandez, J.Ubach, I.Dulubova, X.Zhang, T.C.Südhof, J.Rizo.

Ref.

Cell, 1998, 94, 841-849. [DOI no: 10.1016/S0092-8674(00)81742-0]

PubMed id

9753330

Abstract

Syntaxin 1A plays a central role in neurotransmitter release through multiple protein-protein interactions. We have used NMR spectroscopy to identify an autonomously folded N-terminal domain in syntaxin 1A and to elucidate its three-dimensional structure. This 120-residue N-terminal domain is conserved in plasma membrane syntaxins but not in other syntaxins, indicating a specific role in exocytosis. The domain contains three long alpha helices that form an up-and-down bundle with a left-handed twist. A striking residue conservation is observed throughout a long groove that is likely to provide a specific surface for protein-protein interactions. A highly acidic region binds to the C2A domain of synaptotagmin I in a Ca2+-dependent interaction that may serve as an electrostatic switch in neurotransmitter release.

Figure 1.
Figure 1. Domain Structure of Syntaxins and Sequence Alignment of a Conserved N-Terminal Fragment of Plasma Membrane Syntaxins(a) Schematic diagram of the sequence of syntaxins. Plasma membrane syntaxins contain a transmembrane region (black), a C-terminal sequence of the cytosplasmic region that is involved in formation of the core complex (striped), and an N-terminal region that is likely to have a specific role in exocytosis. The latter is shown in white, with the sequences corresponding to the three helices observed by NMR spectroscopy, HA, HB, and HC, colored in blue, green, and red, respectively. Residue numbers corresponding to the syntaxin 1A sequence are indicated below the bar.(b) The sequence alignment shown corresponds to the segment of the N-terminal region that is autonomously folded in syntaxin 1A. Five of the sequences correspond to Rattus norvegicus syntaxins that have been localized to the plasma membrane (Rn 1A, 1B, 2, 3, and 4), five to syntaxins from other species (Ac, Aplysia californica; Dm, Drosophila melanogaster; Hm, Hirudo medicinalis; Lp, Loligo pealei; Ce, Caenorhabditis elegans) and two sequences are from yeast plasma membrane syntaxins (SSO1 and SSO2). Residue numbers are indicated at the left and the right sides of the sequences. Residues that are identical in at least 6 out of the 12 sequences shown are colored. Blue, green, and red correspond to helix A, B, and C, respectively, and yellow corresponds to residues outside the helices. The bar indicates the sequence of syntaxin 1A involved in binding to the C[2]A domain of synaptotagmin I (see Figure 6).

Figure 3.
Figure 3. Structure of the Nsyx Domain(a) Superposition of the backbone of the 15 simulated annealing structures with the fewest violations from the NMR restraints. The three helices are labeled HA, HB, and HC. The positions of the N and C termini, as well as those of two residues in the loops (residues 69 and 108), are indicated. The backbone atoms of the three helices (residues 28–62, 71–104, and 111–144) were used to superimpose the structures.(b and c) Ribbon diagrams of the structure of Nsyx in two different orientations. Helix A, B, and C are colored in blue, green, and red, respectively. The orientation in (c) results from a 90° rotation of the structure in (b) (pulling the N terminus to the front) and illustrates the left-handed twist of the bundle. The ribbon diagrams were generated with the programs MOLSCRIPT ([29]) and Raster3D ( [37]).

The above figures are reprinted by permission from Cell Press: Cell (1998, 94, 841-849) copyright 1998.