Dpto. Ciencias de la Salud - Osasun Zientziak Saila

Permanent URI for this community

http://hdl.handle.net/2454/10445


Véase además departamentos anteriores a mayo 2018 / Ikus, halaber, 2018ko maiatza baino lehenagoko sailak

Dpto. Producción Agraria - Nekazaritza Ekoizpena Saila

Dpto. Psicología y Pedagogía - Psikologia eta Pedagogia Saila

Dpto. Trabajo Social - Gizarte Lana Saila



Browse

Browsing Dpto. Ciencias de la Salud - Osasun Zientziak Saila by Author "Abramson, Jeff"

Now showing 1 - 3 of 3
  • Thumbnail Image
    PublicationOpen Access
    Affixing N-terminal a-helix to the wall of the voltage-dependent anion channel does not prevent its voltage gating
    (Elsevier, 2012-03-30) Teijido Hermida, Óscar; Ujwal, Rachna; Hillerdal, Carl-Olof; Kullman, Lisen; Rostovtseva, Tatiana K.; Abramson, Jeff; Ciencias de la Salud; Osasun Zientziak
    The voltage-dependent anion channel (VDAC) governs the free exchange of ions and metabolites between the mitochondria and the rest of the cell. The three-dimensional structure of VDAC1 reveals a channel formed by 19 β-strands and an N-terminal α-helix located near the midpoint of the pore. The position of this α-helix causes a narrowing of the cavity, but ample space for metabolite passage remains. The participation of the N-terminus of VDAC1 in the voltage-gating process has been well established, but the molecular mechanism continues to be debated; however, the majority of models entail large conformational changes of this N-terminal segment. Here we report that the pore-lining N-terminal α-helix does not undergo independent structural rearrangements during channel gating. We engineered a double Cys mutant in murine VDAC1 that cross-links the α-helix to the wall of the β-barrel pore and reconstituted the modified protein into planar lipid bilayers. The modified murine VDAC1 exhibited typical voltage gating. These results suggest that the N-terminal α-helix is located inside the pore of VDAC in the open state and remains associated with β-strand 11 of the pore wall during voltage gating
  • Thumbnail Image
    PublicationOpen Access
    A lower affinity to cytosolic proteins reveals VDAC3 isoform-specific role in mitochondrial biology
    (Rockefeller University Press, 2020-01-14) Queralt-Martín, María; Bergdoll, Lucie; Teijido Hermida, Óscar; Munshi, Nabill; Jacobs, Daniel; Kuszak, Adam J.; Protchenko, Olga; Reina, Simona; Magrì, Andrea; De Pinto, Vito; Bezrukov, Sergey M.; Abramson, Jeff; Rostovtseva, Tatiana K.; Ciencias de la Salud; Osasun Zientziak
    Voltage-dependent anion channel (VDAC) is the major pathway for the transport of ions and metabolites across the mitochondrial outer membrane. Among the three known mammalian VDAC isoforms, VDAC3 is the least characterized, but unique functional roles have been proposed in cellular and animal models. Yet, a high-sequence similarity between VDAC1 and VDAC3 is indicative of a similar pore-forming structure. Here, we conclusively show that VDAC3 forms stable, highly conductive voltage-gated channels that, much like VDAC1, are weakly anion selective and facilitate metabolite exchange, but exhibit unique properties when interacting with the cytosolic proteins α-synuclein and tubulin. These two proteins are knowntobepotent regulators of VDAC1 andinduce similar characteristic blockages (on the millisecond time scale) of VDAC3, but with 10- to 100-fold reduced on-rates and altered α-synuclein blocking times, indicative of an isoform-specific function. Through cysteine scanning mutagenesis, we found that VDAC3’s cysteine residues regulate its interaction with α-synuclein, demonstrating VDAC3-unique functional properties and further highlighting a general molecular mechanism for VDAC isoform-specific regulation of mitochondrial bioenergetics.
  • Thumbnail Image
    PublicationOpen Access
    Reply to Thinnes: to include plasmalemmal VDAC/porin pays
    (American Society for Biochemistry and Molecular Biology, 2012-02-06) Teijido Hermida, Óscar; Ujwal, Rachna; Hillerdal, Carl-Olof; Kullman, Lisen; Rostovtseva, Tatiana K.; Abramson, Jeff; Ciencias de la Salud; Osasun Zientziak
    Our study was focused entirely on the properties of VDAC from the mitochondrial outer membrane; therefore, discussion of possible VDAC N-terminal exposure on the plasma membrane surface is totally irrelevant to this work. Our experiments did not aim to test the position of the VDAC1Nterminus in the channel¿s closed conformation. We cannot rule out the possibility that, when closed, the first amino acids of the VDAC N terminus could be exposed at the channel entrance, but these speculations are beyond our present study.