Hi

BRIL is attached to the C-terminal not in the N-terminal.

Best

On Fri, May 23, 2025 at 11:46 AM Firdous Tarique <[email protected]>
wrote:

> Hi everyone
>
> I am encountering an issue during data processing of a membrane protein
> construct fused to BRIL (apocytochrome b562RIL) at the N-terminus. Cryo-EM
> grids were prepared from the same batch of purified protein, but data
> collection was performed at two different time points: one immediately
> after grid preparation, and the other after three years of storage.
>
> In the initial dataset, BRIL is clearly visible in the 2D class averages
> and contributes well to the 3D reconstruction. However, in the dataset
> collected three years later from the same grid batch, no BRIL density is
> observed in either the 2D or 3D reconstructions.
>
> Has anyone observed similar behavior with BRIL fusion constructs,
> particularly the loss of BRIL density over time or during extended sample
> handling? This is my first experience working with BRIL, and I am curious
> whether this could be due to structural degradation, autocleavage, or
> conformational flexibility of the fusion over time.
>
> If anyone is aware of published literature or reports discussing the
> instability or potential autocleavage of BRIL in similar contexts, I would
> greatly appreciate references or insights.
>
> Best wishes
>
> Firdous
>
>
>

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