| Title: |
Docking and molecular dynamics simulations of the Fyn-SH3 domain with free and phospholipid bilayer-associated 18.5-kDa myelin basic protein (MBP) – Insights into a non-canonical and fuzzy interaction |
| Authors: |
Bessonov, Kyrylo; Harauz, George; Vassall, Kenrick |
| Source: |
Proteins (2017-04-12) |
| Publisher Information: |
Wiley Liss, Inc. |
| Publication Year: |
2017 |
| Collection: |
University of Liège: ORBi (Open Repository and Bibliography) |
| Subject Terms: |
molecular dynamics; MBP; docking; Life sciences; Biochemistry; biophysics & molecular biology; Sciences du vivant; Biochimie; biophysique & biologie moléculaire |
| Description: |
peer reviewed ; The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38–S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily-dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a “sandwich”-like structure. In the membrane context, the xα2-peptide interacts with the Fyn-SH3 domain via the proline-rich region and the β-sheets of Fyn-SH3, with the latter wrapping around the proline-rich region in a form of a clip. Moreover, the simulations corroborate prior experimental evidence of the importance of upstream segments beyond the canonical SH3-ligand. This study thus provides a more-detailed glimpse into the context-dependent interaction dynamics and importance of the β-sheets in Fyn-SH3 and proline-rich region of MBP. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
0887-3585; 1097-0134 |
| Relation: |
https://www.synapse.org/#!Synapse:syn5303692/files/; urn:issn:0887-3585; urn:issn:1097-0134; https://orbi.uliege.be/handle/2268/209450; info:hdl:2268/209450; https://orbi.uliege.be/bitstream/2268/209450/1/Fyn_MBP_R1_2017_02_27.pdf; info:pmid:28380689 |
| DOI: |
10.1002/prot.25295 |
| Availability: |
https://orbi.uliege.be/handle/2268/209450; https://orbi.uliege.be/bitstream/2268/209450/1/Fyn_MBP_R1_2017_02_27.pdf; https://doi.org/10.1002/prot.25295 |
| Rights: |
open access ; http://purl.org/coar/access_right/c_abf2 ; info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.EA33649F |
| Database: |
BASE |