The SH3 binding site in front of the WH1 domain contributes to the membrane binding of the BAR domain protein endophilin A2.

The Bin-Amphiphysin-Rvs (BAR) domain of endophilin binds to the cell membrane and shapes it into a tubular shape for endocytosis. Endophilin has a Src-homology 3 (SH3) domain at their C-terminal. The SH3 domain interacts with the proline-rich motif (PRM) that is found in proteins such as neural Wiskott-Aldrich syndrome protein (N-WASP). Here, we re-examined the binding sites of the SH3 domain of endophilin in N-WASP by machine learning-based prediction and identified the previously unrecognized binding site. In addition to the well-recognized PRM at the central proline-rich region, we found a PRM in front of the N-terminal WASP homology 1 (WH1) domain of N-WASP (NtPRM) as a binding site of the endophilin SH3 domain. Furthermore, the diameter of the membrane tubules in the presence of NtPRM mutant was narrower and wider than that in the presence of N-WASP and in its absence, respectively. Importantly, the NtPRM of N-WASP was involved in the membrane localization of endophilin A2 in cells. Therefore, the NtPRM contributes to the binding of endophilin to N-WASP in membrane remodeling. © The Author(s) 2023. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Citation

Pei Fang Sim, Min Fey Chek, Nhung Thi Hong Nguyen, Tamako Nishimura, Takehiko Inaba, Toshio Hakoshima, Shiro Suetsugu. The SH3 binding site in front of the WH1 domain contributes to the membrane binding of the BAR domain protein endophilin A2. Journal of biochemistry. 2023 Dec 20;175(1):57-67

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PMID: 37812440

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