How your muscle cells grab creatine
Probing binding and occlusion of substrate in the human creatine transporter‐1 by computation and mutagenesis
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Surprising Findings
C144 is neutral, not charged—contrary to all prior hypotheses.
Previous models assumed charged residues were essential for substrate binding in SLC6 transporters; this shows the opposite—charging C144 breaks the structure instead of helping.
Practical Takeaways
Researchers can now target D458 or Y148 with chemical chaperones to fix misfolded CRT1 in patients with creatine transporter deficiency.
Not medical advice. For informational purposes only. Always consult a healthcare professional. Terms
Surprising Findings
C144 is neutral, not charged—contrary to all prior hypotheses.
Previous models assumed charged residues were essential for substrate binding in SLC6 transporters; this shows the opposite—charging C144 breaks the structure instead of helping.
Practical Takeaways
Researchers can now target D458 or Y148 with chemical chaperones to fix misfolded CRT1 in patients with creatine transporter deficiency.
Publication
Journal
Protein Science : A Publication of the Protein Society
Year
2023
Authors
Amy Clarke, Clemens V. Farr, Ali El‐Kasaby, D. Szöllősi, M. Freissmuth, S. Sucic, T. Stockner
Related Content
Claims (6)
A specific part of a protein called Y148 grabs onto creatine, while a sodium ion tugs on another part of the protein, and together they snap the transporter shut—like a latch closing to trap creatine inside.
Scientists used a known protein structure to guess how a similar, less-understood protein (CRT1) is shaped, and this guess helps explain why certain broken versions of this protein don’t work right in diseases.
In your body, there’s a tiny protein called CRT1 that helps bring creatine into cells. A specific part of this protein, called D458, needs to be in a neutral (non-charged) state to keep the protein’s structure stable inside the fatty membrane of the cell—if it becomes charged, the structure gets wobbly and lets water leak in where it shouldn’t.
Scientists think a specific part of a protein called CRT1 is probably not charged like they thought before—because if it were charged, it would mess up the protein’s shape and doesn’t really help the protein grab creatine.
To figure out how creatine sticks to its target in the body, scientists need to use super detailed computer simulations—regular docking tools just can’t get it right because they miss key details like how creatine interacts with a specific amino acid and a sodium ion.