TRXL1

TrxL1 is a thioredoxin-fold microtubule inner protein (MIP) that stabilizes the cortical microtubules of Toxoplasma gondii (PMID:23873863, PMID:34031406). Although it associates stably with cortical microtubules, it does not bind them directly; instead it is recruited to the luminal microtubule surface by SPM1, which acts upstream in assembly of the cortical microtubule-coating complex (PMID:23873863). Within this complex TrxL1 co-assembles with its homolog TrxL2 and with SPM1 (PMID:23873863), and cryo-EM shows the three proteins form a luminal mesh that simultaneously reinforces the tubulin lattice in longitudinal and lateral directions (PMID:34031406). Deletion of TrxL1 compromises microtubule stability and integrity under detergent and cold challenge, establishing it as required for cortical microtubule stability (PMID:34031406). Beyond this structural stabilizing role, no catalytic or redox activity for the thioredoxin-like fold has been characterized in the available corpus.

1. 2013 Medium

   Establishing that TrxL1 is a thioredoxin-fold protein stably coating cortical microtubules yet not binding them directly reframed how it must be tethered to the cytoskeleton.

   Evidence Endogenous mEmeraldFP tagging, superresolution imaging, and coimmunoprecipitation in T. gondii

   PMID:23873863

   Open questions at the time

   • No demonstration of any redox or catalytic function for the thioredoxin fold
   • Mechanism of indirect microtubule association not defined at this stage
2. 2013 Medium

   Identifying SPM1 as the recruiter of TrxL1 and defining the SPM1/TrxL2/TrxL1 complex composition resolved the assembly hierarchy of the microtubule-coating complex.

   Evidence Coimmunoprecipitation, mass spectrometry, and fluorescence localization in T. gondii

   PMID:23873863

   Open questions at the time

   • Single-lab Co-IP/MS without reciprocal validation for all partners
   • Functional consequence of the complex on microtubules not yet tested
3. 2021 High

   Cryo-EM structural determination redefined TrxL1 as a bona fide microtubule inner protein forming a luminal mesh that stabilizes the tubulin lattice, explaining its indirect association observed earlier.

   Evidence Single-particle cryo-EM of ex vivo cortical microtubules from T. gondii

   PMID:34031406

   Open questions at the time

   • Contribution of the thioredoxin fold to lattice reinforcement versus a scaffolding role not dissected
   • Whether TrxL1 has any redox chemistry within the lumen unknown
4. 2021 High

   Gene deletion demonstrated that TrxL1 is functionally required for cortical microtubule stability, converting the structural picture into a defined cellular role.

   Evidence Gene deletion with detergent and cold challenge assays in T. gondii

   PMID:34031406

   Open questions at the time

   • Individual contribution of TrxL1 versus TrxL2 and SPM1 to the phenotype not fully separated
   • Downstream effects on parasite motility, invasion, or replication not quantified

• Whether the thioredoxin-like fold of TrxL1 carries any redox or enzymatic activity, or is purely a structural scaffold, remains unresolved.
• No biochemical test of thioredoxin catalytic activity in the corpus
• No identified substrate or redox partner