Lon (also known as endopeptidase La, EC 3.4.21.53) is a multi-domain ATP-dependent protease found throughout all kingdoms of life. It is involved in protein quality control and several regulatory processes. All Lon proteases contain an ATPase domain belonging to the AAA+ superfamily of molecular machines, and a proteolytic domain (see <PDOC51786>) with a serine-lysine catalytic dyad in which a lysine assists the catalytic serine in proteolytic cleavage. Lon proteases can be divided into two subfamilies: A type (A-Lons), which have a large multi-lobed N-terminal domain together with the ATPase and protease domains, and B type (B-Lons), which lack an N domain, but have a membrane-anchoring region emerging from the ATPase domain. B-Lons are found in Archaea, in which they are the lone membrane-anchored ATP-dependent protease. The soluble A-Lons are found in all bacteria and in eukaryotic cell organelles, such as mitochondria and peroxisomes, and are needed for recovery from various stress conditions [1,2,3,4,5,6]. Animal cereblon (CRBN) is a ubiquitously expressed protein that is part of the cullin-4-containing E3 ubiquitin ligase complex CUL4-RBX1-DDB1 (known as CRL4). It contain an N-terminal domain that ressembles the one of A-Lons [7]. The Lon N-terminal domain is thought to be involved in substrate binding and might represent a general protein and polypeptide interaction domain [1,2].

The structure of the Lon N-terminal domain consists of two distinct regions, connected by an extended loop: a compact β-sheet rich, globular subdomain, and an additional α-helical subdomain (see <PDB:3M65>) [1,2].

The profile we developed covers the entire Lon N-terminal domain.