Leucine motifs stabilize residual helical structure in disordered proteins

Zavrtanik, Uroš (avtor), Medved, Tadej (avtor), Purič, Samo (avtor), Vranken, Wim F. (avtor), Lah, Jurij (avtor), Hadži, San (avtor)

Many examples are known of regions of intrinsically disordered proteins that fold into α-helices upon binding to their targets. These helical binding motifs (HBMs) can be partially helical also in the unbound state, and this so-called residual structure can affect binding affinity and kinetics. To investigate the underlying mechanisms governing the formation of residual helical structure, we assembled a dataset of experimental helix contents of 65 peptides containing HBM that fold-upon-binding. The average residual helicity is 17% and increases to 60% upon target binding. The helix contents of residual and target-bound structures do not correlate, however the relative location of helix elements in both states shows a strong overlap. Compared to the general disordered regions, HBMs are enriched in amino acids with high helix preference and these residues are typically involved in target binding, explaining the overlap in helix positions. In particular, we find that leucine residues and leucine motifs in HBMs are the major contributors to helix stabilization and target-binding. For the two model peptides, we show that substitution of leucine motifs to other hydrophobic residues (valine or isoleucine) leads to reduction of residual helicity, supporting the role of leucine as helix stabilizer. From the three hydrophobic residues only leucine can efficiently stabilize residual helical structure. We suggest that the high occurrence of leucine motifs and a general preference for leucine at binding interfaces in HBMs can be explained by its unique ability to stabilize helical elements.

• Jezik: Angleški jezik
• Ključne besede: intrinsically disordered proteins, folding-upon-binding, pre-folding, preotein recognition motif, leucine recognition motif, intrinsic disorder, recognition motif, leucine motif
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FKKT - Fakulteta za kemijo in kemijsko tehnologijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 15 str.
• Številčenje: Vol. 436, iss. 4, art. 168444
• PID: 20.500.12556/RUL-155238
• UDK: 577.322
• ISSN pri članku: 0022-2836
• DOI: 10.1016/j.jmb.2024.168444
• COBISS.SI-ID: 189748995
• Datum objave v RUL: 21.03.2024

Gradivo je del revije

• Naslov: Journal of molecular biology
• Skrajšan naslov: J. mol. biol.
• Založnik: Elsevier
• ISSN: 0022-2836
• COBISS.SI-ID: 25766912

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: intrinzično neurejeni proteini, zvitje ob vezanju, prepoznavni motivi, predzvitje, levcinski prepoznavni motivi