Structures of mycobacterial 3‐methylcrotonyl‐ CoA carboxylase reveal carrier‐domain translocation between catalytic sites

3‐Methylcrotonyl‐CoA carboxylase (MCC) catalyzes an essential step in leucine degradation. Here, we report two high‐resolution cryo‐EM structures of endogenous, biotin‐bound Mycobacterium smegmatis AccA1–AccD1 MCC. The α 6 β 6 complex adopts a canonical architecture with a hexameric carboxyltransferase core flanked by trimeric biotin carboxylase modules. The structures capture BCCP engaged at either the BC or CT active site, revealing long‐range carrier‐domain translocation. In the CT‐engaged state, local BC‐domain shifts disrupt the BC‐site BCCP‐interaction network, disfavoring BCCP rebinding. Unlike human MCC, no comparable CT‐core remodeling is observed, suggesting distinct mechanisms of carrier‐domain coordination.