Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1

NEKULOVÁ, Marta, Marta WYSZKOWSKA, Nela FRIEDLOVÁ, Lukáš UHRÍK, Filip ZAVADIL KOKÁŠ, Václav HRABAL, Lenka HERNYCHOVÁ, Bořivoj VOJTĚŠEK, Ted R. HUPP a Michał SZYMAŃSKI. Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1. BIOLOGICAL CHEMISTRY. GERMANY: WALTER DE GRUYTER GMBH, 2024. ISSN 1431-6730. Dostupné z: https://dx.doi.org/10.1515/hsz-2023-0327.

Základní údaje

• Originální název: Biochemical evidence for conformational variants in the anti-viral and pro-metastatic protein IFITM1
• Autoři: NEKULOVÁ, Marta, Marta WYSZKOWSKA, Nela FRIEDLOVÁ, Lukáš UHRÍK, Filip ZAVADIL KOKÁŠ, Václav HRABAL, Lenka HERNYCHOVÁ, Bořivoj VOJTĚŠEK, Ted R. HUPP a Michał SZYMAŃSKI.
• Vydání: BIOLOGICAL CHEMISTRY, GERMANY, WALTER DE GRUYTER GMBH, 2024, 1431-6730.

Další údaje

• Typ výsledku: Článek v odborném periodiku
• Utajení: není předmětem státního či obchodního tajemství
• Impakt faktor: Impact factor: 3.700 v roce 2022
• Doi: http://dx.doi.org/10.1515/hsz-2023-0327
• Klíčová slova anglicky: hydrogen deuterium exchange; IFITM proteins; oligomerization; protein conformation; protein structure
• Příznaky: Mezinárodní význam, Recenzováno

Anotace anglicky

Interferon induced transmembrane proteins (IFITMs) play a dual role in the restriction of RNA viruses and in cancer progression, yet the mechanism of their action remains unknown. Currently, there is no data about the basic biochemical features or biophysical properties of the IFITM1 protein. In this work, we report on description and biochemical characterization of three conformational variants/oligomeric species of recombinant IFITM1 protein derived from an E. coli expression system. The protein was extracted from the membrane fraction, affinity purified, and separated by size exclusion chromatography where two distinct oligomeric species were observed in addition to the expected monomer. These species remained stable upon re-chromatography and were designated as “dimer” and “oligomer” according to their estimated molecular weight. The dimer was found to be less stable compared to the oligomer using circular dichroism thermal denaturation and incubation with a reducing agent. A two-site ELISA and HDX mass spectrometry suggested the existence of structural motif within the N-terminal part of IFITM1 which might be significant in oligomer formation. Together, these data show the unusual propensity of recombinant IFITM1 to naturally assemble into very stable oligomeric species whose study might shed light on IFITM1 anti-viral and pro-oncogenic functions in cells.