Recombinant Human LETMD1 protein

LETMD1 (LEast Tangentially Moving Domain-containing protein 1) is a conserved eukaryotic protein implicated in mitochondrial dynamics and cellular stress responses. Initially identified through bioinformatic analyses of conserved domain architectures, its gene encodes a ~35 kDa protein containing a unique N-terminal domain with predicted alpha-helical structures and a C-terminal transmembrane region. Phylogenetic studies show LETMD1 orthologs across metazoans, suggesting fundamental biological roles.

Experimental evidence localizes LETMD1 to mitochondrial inner membranes, where it physically interacts with components of the mitochondrial contact site and cristae organizing system (MICOS). This association positions LETMD1 as a potential regulator of cristae morphology, though its exact molecular function remains debated. Recombinant LETMD1 proteins, typically expressed in E. coli or mammalian systems (e.g., HEK293) with N-terminal tags (His, FLAG), enable biochemical characterization. Purified LETMD1 demonstrates ATP-independent membrane-binding capacity in vitro.

Cellular studies reveal that LETMD1 knockdown induces mitochondrial fragmentation, impaired oxidative phosphorylation, and increased ROS production. Paradoxically, some cancer models show LETMD1 overexpression correlates with poor prognosis, while neuronal cells require it for survival during metabolic stress. Structural predictions suggest its helical domains may mediate protein-protein interactions, potentially serving as scaffolds for mitochondrial complexes.

Current research focuses on resolving LETMD1's dual roles in mitochondrial architecture maintenance and context-dependent stress signaling. Its recombinant forms are instrumental for crystallography attempts and interaction screens using pull-down assays. Therapeutic interest emerges from its differential expression in neurodegenerative diseases and cancers, though mechanistic insights remain preliminary. The protein's evolutionary conservation and pleiotropic effects position it as a compelling target for fundamental cell biology investigations.