{PDOC51430}
{PS51430; KAIA_N}
{PS51431; KAIA_C}
{BEGIN}
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* KaiA N- and C-terminal domain profiles *
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Cyanobacteria are  the  most  primitive  organisms  known to exhibit circadian
rhythms. KaiA,  kaiB and kaiC (see <PDOC51146>) constitute the circadian clock
machinery in  cyanobacteria,  and kaiA activates kaiBC expression whereas kaiC
represses it  [1].  Apparent  homologues  of  kaiB  and  kaiC  are found among
noncyanobacterial eubacteria  and  the  archaea. However kaiA appears confined
within the  cyanobacteria,  which  are  the only prokaryotes with demonstrated
circadian rhythms [2].

There are  at  least  two types of kaiA proteins: long and short [2]. The long
versions consist  of  ~300  aminoacyl  residues.  There  is  limited  sequence
conservation in  the  amino-terminal 200 residues of these proteins but a high
degree of conservation in the carboxyl-terminal 100 residues. They thus appear
to contain  two  independently folded domains, the amino and carboxyl regions,
connected by   a   canonical   linker.  The  short  versions  are  essentially
independent carboxyl-terminal domains.

The kaiA  N-terminal  domain  consists  of  a  central five-stranded (beta1 to
beta5) parallel  beta-sheet  flanked  by  two groups of alpha-helices (alpha1,
alpha4 and  alpha2,  alpha3)  packed  on  either side of the beta-sheet and an
additional alpha  helix  (alpha5) lying near the amino terminus of the central
beta-strand (see  <PDB:1R8J>) [2,3]. The structure of the N-terminal domain of
kaiA is  that of a pseudo-receiver domain, similar to those found in bacterial
response regulators.  Although the fold is that of a canonical receiver domain
(see <PDOC50110>),  the  primary  sequence  is  dissimilar,  and  it lacks the
conserved aspartate  residue  necessary  for  phosphorylation. KaiA activation
most likely  involves  direct  protein-protein  interactions of the N-terminal
domain that result in functional modulation of the C-terminal effector domain.
The C-terminal kaiA domain is reponsible for dimer formation, binding to kaiC,
enhancing kaiC  phosphorylation  and generating the circadian oscillations. It
adopts a  novel  all  alpha-helical  homodimeric  structure  (see  <PDB:1Q6A>)
[1,3,4,5]. The  kaiA  C-terminal  domain  contains two parallel helix-hairpin-
helix motifs  that  form  a  four helix bundle, which represents a new protein
folding motif.

The profiles we developed cover the entire kaiA N- and C-terminal domains.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Last update: January 2009 / First entry.

[ 1] Uzumaki T., Fujita M., Nakatsu T., Hayashi F., Shibata H., Itoh N.,
     Kato H., Ishiura M.
     "Crystal structure of the C-terminal clock-oscillator domain of the
     cyanobacterial KaiA protein."
     Nat. Struct. Mol. Biol. 11:623-631(2004).
     PubMed=15170179; DOI=10.1038/nsmb781
[ 2] Williams S.B., Vakonakis I., Golden S.S., LiWang A.C.
     "Structure and function from the circadian clock protein KaiA of
     Synechococcus elongatus: a potential clock input mechanism."
     Proc. Natl. Acad. Sci. U.S.A. 99:15357-15362(2002).
     PubMed=12438647; DOI=10.1073/pnas.232517099
[ 3] Ye S., Vakonakis I., Ioerger T.R., LiWang A.C., Sacchettini J.C.
     "Crystal structure of circadian clock protein KaiA from Synechococcus
     elongatus."
     J. Biol. Chem. 279:20511-20518(2004).
     PubMed=15007067; DOI=10.1074/jbc.M400077200
[ 4] Vakonakis I., Sun J., Wu T., Holzenburg A., Golden S.S., LiWang A.C.
     "NMR structure of the KaiC-interacting C-terminal domain of KaiA, a
     circadian clock protein: implications for KaiA-KaiC interaction."
     Proc. Natl. Acad. Sci. U.S.A. 101:1479-1484(2004).
     PubMed=14749515; DOI=10.1073/pnas.0305516101
[ 5] Vakonakis I., LiWang A.C.
     "Structure of the C-terminal domain of the clock protein KaiA in
     complex with a KaiC-derived peptide: implications for KaiC
     regulation."
     Proc. Natl. Acad. Sci. U.S.A. 101:10925-10930(2004).
     PubMed=15256595; DOI=10.1073/pnas.0403037101

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