Intrinsically disordered region of talin’s FERM domain functions as an initial PIP2 recognition site

• Verfasst von: Buhr, Jannik [VerfasserIn]
• Verfasst von: Franz, Florian [VerfasserIn]
• Verfasst von: Gräter, Frauke [VerfasserIn]
• Titel: Intrinsically disordered region of talin’s FERM domain functions as an initial PIP2 recognition site
• Verf.angabe: Jannik Buhr, Florian Franz, and Frauke Gräter
• E-Jahr: 2023
• Jahr: 4 April 2023
• Umfang: 10 S.
• Fussnoten: Online verfügbar 22. Februar 2023, Artikelversion 4. April 2023 ; Im Titel ist die Zahl 2 tiefgestellt ; Gesehen am 09.06.2023
• Titel Quelle: Enthalten in: Biophysical journal
• Ort Quelle: Cambridge, Mass. : Cell Press, 1960
• Jahr Quelle: 2023
• Band/Heft Quelle: 122(2023), 7 vom: Apr., Seite 1277-1286
• ISSN Quelle: 1542-0086
• DOI: doi:10.1016/j.bpj.2023.02.020
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1848508743

Abstract

Focal adhesions (FAs) mediate the interaction of the cytoskeleton with the extracellular matrix in a highly dynamic fashion. Talin is a central regulator, adaptor protein, and mechano-sensor of FA complexes. For recruitment and firm attachment at FAs, talin’s N-terminal FERM domain binds to phosphatidylinositol 4,5-bisphosphate (PIP2)-enriched membranes. A newly published autoinhibitory structure of talin-1, where the known PIP2 interaction sites are covered up, lead us to hypothesize that a hitherto less examined loop insertion of the FERM domain acts as an additional and initial site of contact. We evaluated direct interactions of talin-1 with a PIP2 membrane by means of atomistic molecular dynamics simulations. We show that this unstructured, 33-residue-long loop strongly interacts with PIP2 and can facilitate further membrane contacts, including the canonical PIP2 interactions, by serving as a flexible membrane anchor. Under force as present at FAs, the extensible FERM loop ensures talin maintains membrane contacts when pulled away from the membrane by up to 7 nm. We identify key basic residues of the anchor mediating the highly dynamic talin-membrane interaction. Our results put forward an intrinsically disordered loop as a key and highly adaptable PIP2 recognition site of talin and potentially other PIP2-binding mechano-proteins.