3IQL

Crystal structure of the rat endophilin-A1 SH3 domain

Summary for 3IQL

• Entry DOI: 10.2210/pdb3iql/pdb
• Related: 2knb
• Descriptor: Endophilin-A1, CHLORIDE ION (3 entities in total)
• Functional Keywords: sh3, endophilin, coiled coil, cytoplasm, endocytosis, lipid-binding, membrane, phosphoprotein, sh3 domain, protein binding
• Biological source: Rattus norvegicus (brown rat,rat,rats)
• Cellular location: Cytoplasm: O35179
• Total number of polymer chains: 2
• Total formula weight: 16034.49

Authors

Trempe, J.F.,Kozlov, G.,Camacho, E.M.,Gehring, K. (deposition date: 2009-08-20, release date: 2009-11-10, Last modification date: 2023-09-06)

Primary citation

Trempe, J.F.,Chen, C.X.,Grenier, K.,Camacho, E.M.,Kozlov, G.,McPherson, P.S.,Gehring, K.,Fon, E.A.
SH3 domains from a subset of BAR proteins define a Ubl-binding domain and implicate parkin in synaptic ubiquitination.
Mol.Cell, 36:1034-1047, 2009

PubMed Abstract: Mutations in the parkin gene are responsible for a common inherited form of Parkinson's disease (PD). Parkin is a RING-type E3 ubiquitin ligase with an N-terminal ubiquitin-like domain (Ubl). We report here that the parkin Ubl binds SH3 domains from endocytic BAR proteins such as endophilin-A with an affinity comparable to proline-rich domains (PRDs) from well-established SH3 partners. The NMR structure of the Ubl-SH3 complex identifies the PaRK extension, a unique C-terminal motif in the parkin Ubl required for SH3 binding and for parkin-mediated ubiquitination of endophilin-A in vitro. In nerve terminals, conditions that promote phosphorylation enhance the interaction between parkin and endophilin-A and increase the levels of ubiquitinated proteins within PRD-associated synaptic protein complexes in wild-type but not parkin knockout brain. The findings identify a pathway for the recruitment of synaptic substrates to parkin with the potential to explain the defects in synaptic transmission observed in recessive forms of PD.

PubMed: 20064468
DOI: 10.1016/j.molcel.2009.11.021

Experimental method

X-RAY DIFFRACTION (1.4 Å)