Can there be some modifications in the inner space - like hydroxyprolines?
Hydroxyls might also have a shifted pKa in a specific milieu and perhaps
coordinate some metals... Or can there be some chemical cross-linking? The
inner space of these bundles is generally "used by Nature" to stabilize the
bundles...
---
Michal Navrátil, PhD



ne 8. 2. 2026 v 3:31 odesílatel Santelli, Eugenio <
[email protected]> napsal:

> It does indeed look like you have extra helices sitting along the x
> direction, especially in the corners of the channels, each spanning
> multiple unit cells, and you see an average density over two directions and
> all possible translations. Since each one of them only sees molecules in
> the main lattice (except maybe within each individual channel), lowering
> the symmetry or processing with a multiple of the unit cell may not help.
>
> If it really bothers you, you could try to soak the crystals in cryo for a
> long time and hope they diffuse out without destroying the crystal.
>
> On Feb 6, 2026, at 6:12 AM, Catherine Back <
> [email protected]> wrote:
>
> Hi All, Thank you so much to everyone for all the suggestions so far. In
> reply: The density appears to form a contiguous gap in the lattice (see
> image attached). The channel just looks too big to be real (in my opinion).
> I didn't loop/freeze
> Hi All,
>
> Thank you so much to everyone for all the suggestions so far. In reply:
>
>
>    - The density appears to form a contiguous gap in the lattice (see
>    image attached). The channel just looks too big to be real (in my opinion).
>    - I didn't loop/freeze the crystals so I can't tell you if they were
>    soft/fragile, but no one mentioned that to me.
>    - Apologies for not mentioning - the res of the initially solved
>    structure = 2.3 Å. R factors for the almost complete structure were
>    0.22/0.27.
>    - I tried forcing it to integrate in P1 in xia2/dials, MR solution was
>    the same.
>    - Xtriage (in Phenix - I'm happy to use either software packages!)
>    said all was fine, bar potentially some ice rings.
>    - Zanuda agreed P212121.
>    - Matthew's coefficient predicted 3 ish copies in the AU...but wasn't
>    certain. Though good point about the solvent content - the coiled coils do
>    have low solvent generally.
>    - If you look carefully at the density the 'blue/green' density
>    repeats every width of the unit cell (34.8 A), so you cannot fit another
>    molecule into the density, because it is essentially only about a quarter
>    of the actual protein, just repeated.
>    - I did try Modelcraft, which tried to model in bits into the density,
>    but it was all incorrect - I'm guessing because the density isn't for the
>    whole molecule.
>    - Similarly with MR - I tried to force Phaser to find more molecules,
>    but to no avail.
>    - Contour level was probably around 1.
>    - I have also looked at the indexing for each of the reprocessing
>    outputs - and as you say Graeme - not all the spots have been picked (see
>    image).
>    - Looking at the lattice viewer of the indexed spots there are a lot
>    of white crosses and  two overlapping patterns? See image attached. Though
>    as you say - could be ice or another xtal?
>
>
> [To confuse us even more we did collect data from another crystal (weirdly
> the same condition) which had different packing - hexagonal, like the
> 'missing' molecules in this one. The res and R factors were really bad
> though, so more data was collected. There was no sign of this lattice
> formation in that data.]
>
> So as you can see this is taking me to (and beyond) the edge of my
> crystallography expertise! However, it's good to be challenged every now
> and then, and my brain is certainly being stretched.
>
> Cheers,
> Catherine
>
>
> Dr Catherine R. Back (she/her)
> Senior Post-doctoral Research Associate
> School of Biochemistry
> University of Bristol
> UK
>
> [email protected]
>
> ------------------------------
> *From:* Graeme Winter <[email protected]>
> *Sent:* 06 February 2026 13:27
> *To:* Catherine Back <[email protected]>
> *Cc:* [email protected] <[email protected]>
> *Subject:* Re: [ccp4bb] Crystal pathology diagnosis please
>
> In a case like this I would not trust the auto processing without question
> (says the original author of said auto processing)
>
> At the very least -
>
> - check over the indexing results - has it caught all the spots or > 90%
> of them
> - look at the indexed and unindexed spots in the reciprocal lattice viewer
> - if the latter are unrelated to the former (e.g. secondary crystal, ice,
> …) then it’s fine - but could be weak spots between strong ones indicating
> a larger cell with near-symmetry
> - look at the images with the integration results overlaid - are all the
> spots measured? Check at various points in the data set
>
> If all the spots are integrated, then xtriage etc. as others have
> suggested, and taking your model and trying refinement in P1 (e.g. pull
> integrated data down, scale in P1 or just use zanuda - also another’s
> suggestion) - also: check that the symmetry determination (logs should be
> there) show the P2?2?2? option as being just as good as the 3 x P2? options
> - if one P2 option is much better could be that the true symmetry is
> different
>
> Essentially looking over all the processing “decisions” with a critical
> eye will help you a lot here, happy to help (off list) if you would like
> more pointers
>
> All the best Graeme
>
>
>
> On Feb 6, 2026, at 5:48 AM, Catherine Back <
> [email protected]> wrote:
>
> Morning All,
>
> My colleague and I are trying to solve the structure of a long, alpha
> helical bundle protein. We thought it had solved well with 2 molecules in
> the AU (which had decent stats), but upon a closer look there are very
> large 'solvent channels' in the lattice, with green/blue density within. It
> looks like there are protein molecules, positioned lengthways to the
> molecules in the AU, within these channels which the autoprocessing (at
> Diamond Light Source) is not picking up. See images attached.
>
> I now have the image files and have been reprocessing them using
> xia2-DIALS in ccp4i2.
>
> I am unsure what kind of crystal pathology we're dealing with here. There
> is no twinning warnings or anything else really that the processing has
> identified. The space group is always identified as P212121, unit cell
> 34.8, 184.8, 202.3, 90.0, 90.0, 90.0.
>
> I've tried quite a few different things to get the software to fit
> molecules into the density, including manually extending the unit cell, but
> all the outputs have been wrong or had really bad stats. I'm wondering if
> the indexing is wrong, but I'm not sure how to sort this. There is clearly
> something going on here, which is either really obvious (that I'm not
> identifying because I'm an idiot) or it's something more complex.
>
> Any ideas/help will be much appreciated.
>
> Best wishes,
> Catherine Back
>
> Dr Catherine R. Back (she/her)
> Senior Post-doctoral Research Associate
> School of Biochemistry
> University of Bristol
> UK
>
> [email protected]
>
>
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