Our paper on the proton-driven secondary active #transporter SbmA for antimicrobial peptides is finally out! We used #cryoEM, #EPR, #MD to show that it resembles and undergoes conformational changes like #ABC transporter TMDs consistent with an alternating-access transport mechanism.
Posts by Chancie T
Here, we critically review the structures of the mitochondrial pyruvate carrier (MPC) in apo and ligand-bound states, highlighting controversies with regard to the orientation in the inner membrane, interpretation of the transport states, and modelling of the inhibitors.
doi.org/10.1016/j.ti...
Amazing work Oli and thanks for sharing.
Characterised members of the human SLC25 mitochondrial family. Members of the mitochondrial carriers are shown in rainbow (blue to red) cartoon and surface representations with their primary substrates shown in sphere representations to scale. Only one paralogue is shown.
Our review on the peculiar properties of mitochondrial carriers of the SLC25 family out: portlandpress.com/biochemj/art...
Pleased to share that the 200 kV reconstructions in this paper have been released today:
1. www.emdataresource.org/EMD-50994
2. www.emdataresource.org/EMD-50995
3. www.emdataresource.org/EMD-50996
4. www.emdataresource.org/EMD-50997
5. www.emdataresource.org/EMD-50998
SolΓ¨neβs 4.5 years of postdoctoral work in our lab (she started just before the corona pandemic) has now been published. A heroic effort that revealed -at the single molecule level- that ATP drives the dissociation of an ECF transporter complex under turnover conditions. See rdcu.be/elTKc
The electron cryo-microscope adapted for use at liquid nitrogen temperatures within its custom-made black box.
A colder frontier in cryo-EM π§ͺπ¬
Chris Russoβs group, inc. Joshua Dickerson, adapted #cryoEM to work at liquid helium temperatures (13 kelvins), where every frame captured contains more information than the equivalent using liquid nitrogen (81 kelvins).
Read more: tinyurl.com/mwwcunkc
#LMBResearch
Our paper is finally out: Molecular basis of pyruvate transport and inhibition of the human mitochondrial pyruvate carrier | Science Advances www.science.org/doi/10.1126/...
#mitochondria #cryo-EM
Instead of competing, the Slotboom @membraneenzymology.bsky.social @unigroningen.bsky.social and Beis labs @imperialcollegeldn.bsky.social teamed up for a more complete story.
We also used #EPR #PELDOR studies and #MDsimulations to propose how protonation affects the conformational ensemble and induces coformational changes allowing the movement of antimicrobial peptides and protons across the #membrane.
The conformational states resemble those found in primary active transporters of the #ABC superfamily, and our bioinformatic analysis shows that SbmA-like peptide transporters (SLiPTs) likely evolved from an ancestral ABC transporter.
We have captured occluded and inward-facing states by #cryoEM elucidating the conformational changes associated with proton binding and substrate translocation.
Check out our new preprint on the bacterial secondary active #transporter SbmA.
The work was a collaboration with Nate Traaseth. Hope the method will help others solve structures of small membrane proteins in multiple conformations. The fusion strategy can be seen as a tribute to the late Ron Kaback, who attempted a similar approach with crystallizing the LacY 30 years ago.
Pictures of a man with grey hair and a bear, a younger woman with shoulder length dark hair and a gallery of images of molecules from the link
At the heart of biology is the mantra: structure dictates function.Biological structures are also beautiful in their intricacy. David Goodsell brought this into public view. As he leaves "Molecule of the Month". here's a huge thank you for helping me see more clearlyπ§ͺ1/2
cdn.rcsb.org/rcsb-pdb/gen...
Using 33 pathogenic variants of citrin we identify crucial elements of the carrier domain required for transport and show that the N-terminal domain is not involved in calcium regulation of transport, but causes a mitochondrial import defect, when mutated.
www.sciencedirect.com/science/arti...
Our new paper is out! #mitochondria #transporters #adeninetranslocase #SLC25
www.science.org/doi/10.1126/...
Could you add me too? Thanks.
I would like to be added as well. Thank you.