Unique structural organization of ATP-dependent LonA proteases

Abstract

Homooligomeric LonA proteases are the key components of the protein quality control system in bacteria and eukaryotes. Domain organization of the common pool of LonA proteases is determined by comparative analysis of primary and secondary structures of a number of bacterial and eukaryotic enzymes. The similarity of individual enzyme domains was estimated, domain-domain linker areas were revealed, regions that are capable to include intercalated peptide fragments were identified. LonA proteases were shown to be unique AAA+ proteins, because in addition to the classic AAA+ module they contain a part of another AAA+ module, namely the alpha-helical domain including a coiled-coil region, which is similar to the alpha-helical domain of the AAA(+)-1 module of the chaperone-disagregases ClpB/Hsp104.

New insights into structural and functional relationships between LonA proteases and ClpB chaperones

“…Whereas a resemblance of the HI(CC) domain of LonA to the H1(M) fragment of ClpB has been previously suggested , no structural basis for such a topological similarity has been established. A comparison of the primary and secondary structures of the HI(CC) domains of Ec Lon, Bs Lon, and Mt Lon on the one hand, and the H1(M) fragments of E. coli and Thermus thermophilus ClpB chaperones ( Ec ClpB and Tt ClpB) on the other hand (Fig.…”

“…Structural data are available for two N‐terminal fragments of Ec Lon, consisting of 116 and 245 amino acid residues, respectively , as well as for a fragment of Bs Lon (1–209) . These structures, combined with prediction of the secondary structures for several other LonA proteases (http://www.ch.embnet.org), revealed that the extended N‐terminal region of LonA proteases preceding the AAA + module is formed by two domains, the predominantly β‐structured N domain, and the α‐helical HI(CC) domain (Figs and ) .…”

“…One of the helices in the M domain is composed of 58 residues, similar to the long a7 helix in the EcLon HI(CC) domain. This resemblance prompted a conjecture that the HI(CC) domain might correspond to an a-helical domain of a hypothetical AAA + module that has lost its own NB domain, and is embedded between the N domain and the existing single AAA + module of LonA [18]. This conjecture is supported by the prior observation that organization of the sole ATPase modules in the class II AAA + proteins (ClpX and HslU) is similar to the organization of the D2 modules in the class I AAA + proteins [13,[50][51][52][53].…”

“…It has been suggested that the N‐terminal region represents a combination of two domains—the actual N‐terminal (N) domain, followed by an inserted domain which is located between the N domain and the AAA + module . This inserted domain, referred to as HI(CC) (helical inserted with CC‐fragment , Fig. ), is formed exclusively by α‐helices and is predicted to contain a CC fragment (see also https://embnet.vital-it.ch/software/COILS_form.html).…”

“…It was suggested that the HI(CC) domain resembles the H1 domain of ClpB chaperone, which also contains a fragment of similar size with CC conformation (namely M domain, Fig. ) .…”