4JEH

Crystal Structure of Munc18a and Syntaxin1 lacking N-peptide complex

Summary for 4JEH

• Entry DOI: 10.2210/pdb4jeh/pdb
• Related: 4JEU
• Descriptor: Syntaxin-binding protein 1, Syntaxin-1A (3 entities in total)
• Functional Keywords: protein complex, membrane, phosphoprotein, protein transport, transport, neurotransmitter transport, transmembrane, endocytosis-exocytosis complex, endocytosis/exocytosis
• Biological source: Rattus norvegicus (rat); More
• Cellular location: Cytoplasm: P61765; Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type IV membrane protein (By similarity): P32851
• Total number of polymer chains: 2
• Total formula weight: 97591.46

Authors

Colbert, K.N.,Hattendorf, D.A.,Weiss, T.M.,Burkhardt, P.,Fasshauer, D.,Weis, W.I. (deposition date: 2013-02-27, release date: 2013-07-17, Last modification date: 2023-09-20)

Primary citation

Colbert, K.N.,Hattendorf, D.A.,Weiss, T.M.,Burkhardt, P.,Fasshauer, D.,Weis, W.I.
Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation.
Proc.Natl.Acad.Sci.USA, 110:12637-12642, 2013

PubMed Abstract: In neurons, soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins drive the fusion of synaptic vesicles to the plasma membrane through the formation of a four-helix SNARE complex. Members of the Sec1/Munc18 protein family regulate membrane fusion through interactions with the syntaxin family of SNARE proteins. The neuronal protein Munc18a interacts with a closed conformation of the SNARE protein syntaxin1a (Syx1a) and with an assembled SNARE complex containing Syx1a in an open conformation. The N-peptide of Syx1a (amino acids 1-24) has been implicated in the transition of Munc18a-bound Syx1a to Munc18a-bound SNARE complex, but the underlying mechanism is not understood. Here we report the X-ray crystal structures of Munc18a bound to Syx1a with and without its native N-peptide (Syx1aΔN), along with small-angle X-ray scattering (SAXS) data for Munc18a bound to Syx1a, Syx1aΔN, and Syx1a L165A/E166A (LE), a mutation thought to render Syx1a in a constitutively open conformation. We show that all three complexes adopt the same global structure, in which Munc18a binds a closed conformation of Syx1a. We also identify a possible structural connection between the Syx1a N-peptide and SNARE domain that might be important for the transition of closed-to-open Syx1a in SNARE complex assembly. Although the role of the N-peptide in Munc18a-mediated SNARE complex assembly remains unclear, our results demonstrate that the N-peptide and LE mutation have no effect on the global conformation of the Munc18a-Syx1a complex.

PubMed: 23858467
DOI: 10.1073/pnas.1303753110

Experimental method

X-RAY DIFFRACTION (2.5 Å)