The Minimum Protein Staple? – Towards ‘bio’-Baldwin's rules <i>via</i> inter-phosphosite linking in the MEK1 activation loop

Journal article

electrophilic site in just one of two regioisomeric potential precursors to allow phosphosite-to-phosphosite 'stapling'. This first example of spontaneous protein thioether ring-closing/'stapling' and its accessibility from just one precursor (despite the potential for both to form an identical 'staple') now reveals the potential for Lan formation not only as an accessible form of minimal stapling in proteins but also as an exquisitely sensitive probe of associated protein geometries. We suggest that the use of this (as well as the development of other such, intramolecular protein traps that are dependent on inherent protein-controlled reactivity rather than forced crosslinking) may allow the broader trapping and mapping of relevant, even minor, protein states. In this way, protein ring formation may enable a form of extended 'bio-Baldwin's rules' that help to delineate relevant protein conformational space.

Authors: Galan, SRG; Raj, R; Mamalis, D; Jones, LH; Mohammed, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Royal Society of Chemistry
• Journal: Chemical Science
• Volume: 15
• Issue: 4
• Pages: 1306-1317
• Publication date: 2024-01-24
• DOI: 10.1039/d3sc04631a
• EISSN: 2041-6539
• ISSN: 2041-6520
• Language: English
• Keywords: Mathematics; Chemistry; Biology; Cell biology; Loop (graph theory); Combinatorics