Segmentation strategy of de novo designed four-helical bundles expands protein oligomerization modalities for cell regulation

Merljak, Estera (avtor), Malovrh, Benjamin (avtor), Jerala, Roman (avtor)

Protein–protein interactions govern most biological processes. New protein assemblies can be introduced through the fusion of selected proteins with di/oligomerization domains, which interact specifically with their partners but not with other cellular proteins. While four-helical bundle proteins (4HB) have typically been assembled from two segments, each comprising two helices, here we show that they can be efficiently segmented in various ways, expanding the number of combinations generated from a single 4HB. We implement a segmentation strategy of 4HB to design two-, three-, or four-chain combinations for the recruitment of multiple protein components. Different segmentations provide new insight into the role of individual helices for 4HB assembly. We evaluate 4HB segmentations for potential use in mammalian cells for the reconstitution of a protein reporter, transcriptional activation, and inducible 4HB assembly. Furthermore, the implementation of trimerization is demonstrated as a modular chimeric antigen receptor for the recognition of multiple cancer antigens.

• Jezik: Angleški jezik
• Ključne besede: molecular engineering, synthetic biology
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: 12 str.
• Številčenje: Vol. 14, art. 1995
• PID: 20.500.12556/RUL-155351
• UDK: 577
• ISSN pri članku: 2041-1723
• DOI: 10.1038/s41467-023-37765-6
• COBISS.SI-ID: 150022147
• Datum objave v RUL: 27.03.2024

Gradivo je del revije

• Naslov: Nature communications
• Skrajšan naslov: Nat. Commun.
• Založnik: Nature Publishing Group
• ISSN: 2041-1723
• COBISS.SI-ID: 2315876

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: biokemija, proteini, beljakovine, antigenski receptorji, rakava obolenja

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P4-0176
• Naslov: Molekularna biotehnologija: od dinamike bioloških sistemov do aplikacij