LYRM2

Model summary

A soluble mitochondrial assembly factor that uses a LYR-module scaffold to bind and stabilize early intermediates of the NADH:ubiquinone oxidoreductase. By organizing protein–protein interfaces rather than catalyzing reactions, it promotes orderly biogenesis of the respiratory chain’s entry complex at the inner-membrane interface, thereby supporting efficient maturation and stability of the assembled enzyme within mitochondria.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The polypeptide carries IPR045293 (LYRM2, LYR domain, residues 17–79) and IPR008011 (Complex I LYR protein domain, residues 20–78). The two signatures overlap almost entirely, indicating a single LYR-type module that defines the protein’s biochemical and assembly roles. LYR domains are compact, soluble assembly factors that use an N-terminal LYR motif and adjacent helical elements to mediate avid protein–protein interactions rather than catalysis. This architecture causes a binding-centric molecular function: the LYR module forms a docking surface that stabilizes assembly intermediates and recruits partner proteins, consistent with GO:0005515 protein binding as the primary molecular function.

2. 02

   From this binding-centric core, I infer the biological process.

   LYR-family proteins are canonically dedicated to mitochondrial respiratory chain complex I biogenesis. The explicit Complex I LYR domain (IPR008011) ties the LYR module to assembly steps of the NADH:ubiquinone oxidoreductase. Such a role naturally drives GO:0032981 mitochondrial respiratory chain complex I assembly. The causal chain is: the LYR domain confers high-affinity assembly contacts; these contacts nucleate and stabilize early complex I subassemblies; stabilization promotes maturation of the holoenzyme.

3. 03

   Cellular localization follows from where complex I is built and where LYR assembly factors operate.

   Complex I is built and resides at the mitochondrial inner membrane, with assembly modules straddling the matrix side and inner-membrane-proximal regions. The LYR architecture lacks transmembrane segments and therefore acts as a soluble assembly cofactor that associates with the inner-membrane-embedded complex. This places the protein functionally at GO:0005747 mitochondrial respiratory chain complex I and supports a mitochondrial localization.

4. 04

   Mechanistically, the LYR domain provides a scaffold that organizes early assembly modules and coordinates cofactor delivery.

   By binding nascent complex I subunits and assembly chaperones, it stabilizes intermediates and prevents premature dissociation. I hypothesize that it transiently associates with core and accessory complex I subunits (for example, NDUFS and NDUFV modules) and with matrix-exposed assembly factors that shepherd biogenesis. Through these interactions, it promotes orderly assembly at the inner membrane interface, ensuring efficient maturation of the respiratory chain’s entry complex.