Falcon (Edison) deep research report for S. pombe atg101 (autophagy initiation; Atg13-binding HORMA subunit of the Atg1 complex)
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Atg101 forms an obligate HORMA heterodimer with the Atg13 HORMA domain that stabilizes both partners, providing a structural adaptor module within the Atg1 initiation complex.
"Their heterodimerization is obligate and stabilizes both partners, providing a structural module within the initiation complex."
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Differential scanning fluorimetry quantifies the stabilization: Atg13HORMA Tm ~43 C and Atg101 ~48 C alone, rising to ~63 C for the heterodimer.
"Differential scanning fluorimetry melting temperatures (Tm): **Atg13HORMA ~43°C**, **Atg101 ~48°C**, and **Atg13HORMA–Atg101 complex ~63°C**."
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In S. pombe Atg101 binds the Atg13 HORMA domain (and contacts the Atg1 C-terminal domain) but does not bind Atg17, incorporating into the complex via Atg13.
"showed that Atg101 does **not** bind Atg17, but **does** bind Atg13’s HORMA domain and can interact with the Atg1 C‑terminal domain (Atg1CTD), indicating incorporation into the complex via Atg13 and additional contacts."
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Beyond Atg13 binding, a conserved WF finger contributes separable function; a WF-finger triple mutant retains Atg13 binding but impairs autophagy.
"A **WF-finger triple mutant (W110A, P111A, F112A)** retained Atg13 binding but **impaired autophagy**, indicating Atg101 has functional roles beyond stabilizing/binding Atg13."
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In S. pombe Atg101 is dispensable for Atg1 kinase activation in vitro; Atg1 from atg101-delta cells autophosphorylates like wild type.
"Atg1 purified from **atg101Δ** cells showed **autophosphorylation activity similar to wild type** under both nutrient-rich and nitrogen-starvation conditions."
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Direct S. pombe Atg101 subcellular localization was not established in the retrieved primary literature; localization is inferred from complex membership and mammalian analogy.
"Direct evidence for *S. pombe* Atg101 localization (e.g., PAS puncta, cytosolic vs membrane recruitment) was not found in the retrieved full texts."
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The sporulation/mug66 phenotype is interpreted as an indirect consequence of autophagy deficiency rather than a direct meiotic role.
"Since autophagy is required for spore formation in both budding and fission yeast, the paper suggests the sporulation defect “may be due to a deficiency in autophagy.”"