Database accession: MF7000124
Name: Endophilin A1 BAR domain (rat)
PDB ID: 2c08
Experimental method: X-ray (2.90 Å)
Assembly: Homodimer
Source organism: Rattus norvegicus
Primary publication of the structure:
Gallop JL, Jao CC, Kent HM, Butler PJ, Evans PR, Langen R, McMahon HT
Mechanism of endophilin N-BAR domain-mediated membrane curvature.
(2006) EMBO J. 25: 2898-910
PMID: 16763559
Abstract:
Endophilin-A1 is a BAR domain-containing protein enriched at synapses and is implicated in synaptic vesicle endocytosis. It binds to dynamin and synaptojanin via a C-terminal SH3 domain. We examine the mechanism by which the BAR domain and an N-terminal amphipathic helix, which folds upon membrane binding, work as a functional unit (the N-BAR domain) to promote dimerisation and membrane curvature generation. By electron paramagnetic resonance spectroscopy, we show that this amphipathic helix is peripherally bound in the plane of the membrane, with the midpoint of insertion aligned with the phosphate level of headgroups. This places the helix in an optimal position to effect membrane curvature generation. We solved the crystal structure of rat endophilin-A1 BAR domain and examined a distinctive insert protruding from the membrane interaction face. This insert is predicted to form an additional amphipathic helix and is important for curvature generation. Its presence defines an endophilin/nadrin subclass of BAR domains. We propose that N-BAR domains function as low-affinity dimers regulating binding partner recruitment to areas of high membrane curvature.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
identical protein binding identical protein binding
lipid binding lipid binding
protein kinase binding protein kinase binding
transmembrane transporter binding transmembrane transporter binding
Biological process:
cellular response to brain-derived neurotrophic factor stimulus cellular response to brain-derived neurotrophic factor stimulus
dendrite extension dendrite extension
lipid tube assembly lipid tube assembly
membrane bending membrane bending
membrane tubulation membrane tubulation
negative regulation of blood-brain barrier permeability negative regulation of blood-brain barrier permeability
negative regulation of gene expression negative regulation of gene expression
negative regulation of protein phosphorylation negative regulation of protein phosphorylation
neuron projection development neuron projection development
positive regulation of membrane tubulation positive regulation of membrane tubulation
postsynaptic actin cytoskeleton organization postsynaptic actin cytoskeleton organization
regulation of clathrin-dependent endocytosis regulation of clathrin-dependent endocytosis
regulation of receptor internalization regulation of receptor internalization
synaptic vesicle endocytosis synaptic vesicle endocytosis
synaptic vesicle uncoating synaptic vesicle uncoating
vesicle scission vesicle scission
Cellular component:
basal dendrite basal dendrite
cytoplasm cytoplasm
early endosome early endosome
glutamatergic synapse glutamatergic synapse
hippocampal mossy fiber to CA3 synapse hippocampal mossy fiber to CA3 synapse
neuronal cell body neuronal cell body
perinuclear region of cytoplasm perinuclear region of cytoplasm
photoreceptor ribbon synapse photoreceptor ribbon synapse
plasma membrane plasma membrane
postsynapse postsynapse
presynapse presynapse
presynaptic cytosol presynaptic cytosol
Schaffer collateral - CA1 synapse Schaffer collateral - CA1 synapse
synapse synapse
synaptic vesicle membrane synaptic vesicle membrane
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Endophilin-A1
Source organism: Rattus norvegicus
Length: 352 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSVAGLKKQFHKATQKVSEKVGGAEGTKLDDDFKEMERKVDVTSRAVMEIMTKTIEYLQPNPASRAKLSMINTMSKIRGQEKGPGYPQAEALLAEAMLKFGRELGDDCNFGPALGEVGEAMRELSEVKDSLDMEVKQNFIDPLQNLHDKDLREIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFDESKEIAESSMFNLLEMDIEQVSQLSALVQAQLEYHKQAVQILQQVTVRLEERIRQASSQPRREYQPKPRMSLEFATGDGTQPNGGLSHTGTPKPAGVQMDQPCCRALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMLHGQSGFFPINYVEILVALPH
UniProtKB AC: O35179 (positions: 25-247)
Coverage: 63%
Name: Endophilin-A1
Source organism: Rattus norvegicus
Length: 352 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSVAGLKKQFHKATQKVSEKVGGAEGTKLDDDFKEMERKVDVTSRAVMEIMTKTIEYLQPNPASRAKLSMINTMSKIRGQEKGPGYPQAEALLAEAMLKFGRELGDDCNFGPALGEVGEAMRELSEVKDSLDMEVKQNFIDPLQNLHDKDLREIQHHLKKLEGRRLDFDYKKKRQGKIPDEELRQALEKFDESKEIAESSMFNLLEMDIEQVSQLSALVQAQLEYHKQAVQILQQVTVRLEERIRQASSQPRREYQPKPRMSLEFATGDGTQPNGGLSHTGTPKPAGVQMDQPCCRALYDFEPENEGELGFKEGDIITLTNQIDENWYEGMLHGQSGFFPINYVEILVALPH
UniProtKB AC: O35179 (positions: 25-247)
Coverage: 63%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: N-BAR domain
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
The human AmphyphisinII/Bin1 and Endophilin BAR domains (N-BARs) display two-state equilibrium unfolding from the dimeric to unfolded monomeric forms (PMID:26368922, PMID:34423187).
Chain A:
N/A
Chain A-2:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
