4jeh

Crystal Structure of Munc18a and Syntaxin1 lacking N-peptide complexCrystal Structure of Munc18a and Syntaxin1 lacking N-peptide complex

Structural highlights 4jeh is a 2 chain structure with sequence from Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Related: 4jeu Gene: Stxbp1, Unc18a (Rattus norvegicus), Stx1a, Sap (Rattus norvegicus) Resources: FirstGlance, OCA, RCSB, PDBsum Function [STXB1_RAT] May participate in the regulation of synaptic vesicle docking and fusion, possibly through interaction with GTP-binding proteins. Essential for neurotransmission and binds syntaxin, a component of the synaptic vesicle fusion machinery probably in a 1:1 ratio. Can interact with syntaxins 1, 2, and 3 but not syntaxin 4. May play a role in determining the specificity of intracellular fusion reactions. [STX1A_RAT] Potentially involved in docking of synaptic vesicles at presynaptic active zones. May play a critical role in neurotransmitter exocytosis. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm. Publication Abstract from PubMed 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 (Syx1aDeltaN), along with small-angle X-ray scattering (SAXS) data for Munc18a bound to Syx1a, Syx1aDeltaN, 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. Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation.,Colbert KN, Hattendorf DA, Weiss TM, Burkhardt P, Fasshauer D, Weis WI Proc Natl Acad Sci U S A. 2013 Jul 30;110(31):12637-42. doi:, 10.1073/pnas.1303753110. Epub 2013 Jul 15. PMID:23858467 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4jeh, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image