The binding of syndapin SH3 domain to dynamin proline-rich domain involves short and long distance elements

Luo, Lin, Xue, Jing, Kwan, Ann, Gamsjaeger, Roland, Wielens, Jerome, von Kleist, Lisa, Cubeddu, Liza, Guo, Zhong, Stow, Jennifer L., Parker, Michael W., Mackay, Joel P. and Robinson, Phillip J. (2016) The binding of syndapin SH3 domain to dynamin proline-rich domain involves short and long distance elements. Journal of Biological Chemistry, 291 18: 9411-+. doi:10.1074/jbc.M115.703108

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Author Luo, Lin
Xue, Jing
Kwan, Ann
Gamsjaeger, Roland
Wielens, Jerome
von Kleist, Lisa
Cubeddu, Liza
Guo, Zhong
Stow, Jennifer L.
Parker, Michael W.
Mackay, Joel P.
Robinson, Phillip J.
Title The binding of syndapin SH3 domain to dynamin proline-rich domain involves short and long distance elements
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2016-04-01
Year available 2016
Sub-type Article (original research)
DOI 10.1074/jbc.M115.703108
Open Access Status File (Publisher version)
Volume 291
Issue 18
Start page 9411
End page +
Total pages 16
Place of publication Bethesda, MD United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Subject 1303 Biochemistry
1312 Molecular Biology
1307 Cell Biology
Abstract Dynamin is a GTPase that mediates vesicle fission during synaptic vesicle endocytosis. Its long C-terminal proline-rich domain contains 13 PXXP motifs, which orchestrate its interactions with multiple proteins. The SH3 domains of syndapin and endophilin bind the PXXP motifs called Site 2 and 3 (Pro-786–Pro-793) at the N-terminal end of the proline-rich domain, whereas the amphiphysin SH3 binds Site 9 (Pro-833–Pro-836) toward the C-terminal end. In some proteins, SH3/peptide interactions also involve short distance elements, which are 5–15 amino acid extensions flanking the central PXXP motif for high affinity binding. Here we found two previously unrecognized elements in the central and the C-terminal end of the dynamin proline-rich domain that account for a significant increase in syndapin binding affinity compared with a previously reported Site 2 and Site 3 PXXP peptide alone. The first new element (Gly-807–Gly-811) is short distance element on the C-terminal side of Site 2 PXXP, which might contact a groove identified under the RT loop of the SH3 domain. The second element (Arg-838–Pro-844) is located about 50 amino acids downstream of Site 2. These two elements provide additional specificity to the syndapin SH3 domain outside of the well described polyproline-binding groove. Thus, the dynamin/syndapin interaction is mediated via a network of multiple contacts outside the core PXXP motif over a previously unrecognized extended region of the proline-rich domain. To our knowledge this is the first example among known SH3 interactions to involve spatially separated and extended long-range elements that combine to provide a higher affinity interaction.
Keyword Dynamin
Endocytosis
Nuclear magnetic resonance (NMR)
Src homology 3 domain (SH3 domain)
Structural model
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID GNT1047070
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
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