{PDOC51787}
{PS51787; LON_N}
{BEGIN}
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* Lon N-terminal domain profile *
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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 beta-sheet rich, globular subdomain,
and an additional alpha-helical subdomain (see <PDB:3M65>) [1,2].

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

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2023 / Profile revised.

[ 1] Duman R.E., Loewe J.
     "Crystal structures of Bacillus subtilis Lon protease."
     J. Mol. Biol. 401:653-670(2010).
     PubMed=20600124; DOI=10.1016/j.jmb.2010.06.030
[ 2] Li M., Rasulova F., Melnikov E.E., Rotanova T.V., Gustchina A.,
     Maurizi M.R., Wlodawer A.
     "Crystal structure of the N-terminal domain of E. coli Lon protease."
     Protein Sci. 14:2895-2900(2005).
     PubMed=16199667; DOI=10.1110/ps.051736805
[ 3] Botos I., Melnikov E.E., Cherry S., Kozlov S., Makhovskaya O.V.,
     Tropea J.E., Gustchina A., Rotanova T.V., Wlodawer A.
     "Atomic-resolution crystal structure of the proteolytic domain of
     Archaeoglobus fulgidus lon reveals the conformational variability in
     the active sites of lon proteases."
     J. Mol. Biol. 351:144-157(2005).
[ 4] Rotanova T.V., Botos I., Melnikov E.E., Rasulova F., Gustchina A.,
     Maurizi M.R., Wlodawer A.
     "Slicing a protease: structural features of the ATP-dependent Lon
     proteases gleaned from investigations of isolated domains."
     Protein Sci. 15:1815-1828(2006).
     PubMed=16877706; DOI=10.1110/ps.052069306
[ 5] Cha S.-S., An Y.J., Lee C.R., Lee H.S., Kim Y.-G., Kim S.J., Kwon K.K.,
     De Donatis G.M., Lee J.-H., Maurizi M.R., Kang S.G.
     "Crystal structure of Lon protease: molecular architecture of gated
     entry to a sequestered degradation chamber."
     EMBO J. 29:3520-3530(2010).
     PubMed=20834233; DOI=10.1038/emboj.2010.226
[ 6] Garcia-Nafria J., Ondrovicova G., Blagova E., Levdikov V.M.,
     Bauer J.A., Suzuki C.K., Kutejova E., Wilkinson A.J., Wilson K.S.
     "Structure of the catalytic domain of the human mitochondrial Lon
     protease: proposed relation of oligomer formation and activity."
     Protein Sci. 19:987-999(2010).
     PubMed=20222013; DOI=10.1002/pro.376
[ 7] Fischer E.S., Boehm K., Lydeard J.R., Yang H., Stadler M.B.,
     Cavadini S., Nagel J., Serluca F., Acker V., Lingaraju G.M.,
     Tichkule R.B., Schebesta M., Forrester W.C., Schirle M., Hassiepen U.,
     Ottl J., Hild M., Beckwith R.E.J., Harper J.W., Jenkins J.L.,
     Thomae N.H.
     "Structure of the DDB1-CRBN E3 ubiquitin ligase in complex with
     thalidomide."
     Nature 512:49-53(2014).
     PubMed=25043012; DOI=10.1038/nature13527

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