📝 Online now - the Review "Membranes as targets and modifiers of mutant huntingtin aggregation" from Justin Legleiter.

#HuntingtonsDisease #polyglutamine #amyloid #lipidbinding #neurodegeneration

Read it here 👉 authors.elsevier.com/a/1ll3e_M0e4...

1️⃣8️⃣ Caspase-11 Detects Lipids via Two Cues
Caspase-11 recognizes lipids with ≥14C acyl chains and a negatively charged phosphate headgroup. Chimeric proteins converting AcCARD and TIRAP-CARD support this bipartite model. #Immunology #Caspase11 #LipidBinding

🔟 Acyl Chain Binding is Conserved Across Mammals
PGPC protected 16 of 22 caspase-4 CARDs. Phe45 and Phe76 were enriched in PGPC-protected CARDs, but some protected variants lacked both, suggesting additional binding determinants. #Immunology #Caspase4 #LipidBinding

9️⃣ Acyl Chain Length Determines Binding
To examine the role of acyl chain length, we tested LysoPCs (6–18 carbons). Only LysoPCs with ≥14 carbons protected caspase-11. This protective effect also occurred with the CARD, similar to LPS and PGPC interactions. #Immunology #Caspase11 #LipidBinding

6️⃣ Trypsin Resistance Reveals Ligand Binding
Unbound caspase-11 degrades to a 20 kDa fragment within 15 min. However, LPS-EB, LPS-RS, and PGPC induce a trypsin-resistant state, yielding a 35 kDa band, suggesting ligand binding alters caspase-11 conformation. #ProteinStructure #LipidBinding