6H5T

Intersectin SH3A short isoform


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.69 Å
  • R-Value Free: 0.191 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.176 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain.

Gerth, F.Japel, M.Sticht, J.Kuropka, B.Schmitt, X.J.Driller, J.H.Loll, B.Wahl, M.C.Pagel, K.Haucke, V.Freund, C.

(2019) Structure 27: 977

  • DOI: https://doi.org/10.1016/j.str.2019.03.020
  • Primary Citation of Related Structures:  
    6H5T

  • PubMed Abstract: 

    The scaffolding protein intersectin 1 plays important roles in clathrin-mediated endocytosis and in the replenishment of release-ready synaptic vesicles (SV). Two splice variants of intersectin's SH3A domain are expressed in the brain, and association of the neuron-specific variant with synapsin I has been shown to enable sustained neurotransmission and to be regulated by an adjacent C-terminal motif. Here, we demonstrate that the ubiquitously expressed short SH3A variant of intersectin 1 interacts with an N-terminal intramolecular sequence that operates synergistically with the C-terminal motif. NMR spectroscopic investigations show that the five-amino acid insertion into the β strand 2 of the neuronal SH3A variant introduces conformational plasticity incompatible with binding of the N-terminal sequence. The difference in the autoregulatory mechanism of the domain's variants differentially affects its synaptic binding partners, thereby establishing alternative splicing in conjunction with autoinhibitory motif variation as a mechanism to regulate protein interaction networks.


  • Organizational Affiliation

    Protein Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Intersectin-1
A, B
99Homo sapiensMutation(s): 0 
Gene Names: ITSN1ITSNSH3D1A
UniProt & NIH Common Fund Data Resources
Find proteins for Q15811 (Homo sapiens)
Explore Q15811 
Go to UniProtKB:  Q15811
PHAROS:  Q15811
GTEx:  ENSG00000205726 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15811
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
7PG
Query on 7PG

Download Ideal Coordinates CCD File 
C [auth A],
G [auth B]
2,5,8,11,14,17,20,23-OCTAOXAPENTACOSAN-25-OL
C17 H36 O9
SZGNWRSFHADOMY-UHFFFAOYSA-N
ZN
Query on ZN

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
I [auth B]
ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
ACT
Query on ACT

Download Ideal Coordinates CCD File 
H [auth B]ACETATE ION
C2 H3 O2
QTBSBXVTEAMEQO-UHFFFAOYSA-M
CL
Query on CL

Download Ideal Coordinates CCD File 
D [auth A]CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Experimental Data & Validation

Experimental Data

Unit Cell:
Length ( Å )Angle ( ˚ )
a = 86.792α = 90
b = 86.792β = 90
c = 141.768γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
SHARPphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
German Research FoundationGermanySFB958

Revision History  (Full details and data files)

  • Version 1.0: 2019-02-27
    Type: Initial release
  • Version 1.1: 2019-05-08
    Changes: Data collection, Database references
  • Version 1.2: 2019-05-15
    Changes: Data collection
  • Version 1.3: 2019-06-19
    Changes: Data collection, Database references
  • Version 1.4: 2019-08-21
    Changes: Data collection, Database references
  • Version 1.5: 2024-05-15
    Changes: Data collection, Database references, Derived calculations