{PDOC51789}
{PS51789; RLR_CTR}
{BEGIN}
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* RIG-I-like receptor (RLR) C-terminal regulatory (CTR) domain profile *
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Intracellular RIG-I-like  receptors  (RLRs:  retinoic  acid-inducible  gene I,
RIG-I; melanoma  differenciation-associated  gene  5, MDA-5; and laboratory of
genetics and  physiology  2, LGP2) recognize viral RNAs as pathogen-associated
molecular patterns  (PAMPs)  and  initiate  an antiviral immune response. RLRs
belong to  the  superfamily  2  (SF2) helicases or ATPases. Among SF2 ATPases,
RIG-I, MDA5,  and  LGP2  possess  a  unique  domain  structure. RIG-I and MDA5
consist of  two  N-terminal caspase activation and recruitment domains (CARDs)
(see <PDOC50209>),  a  central  SF2 type DECH box ATPase domain (consisting of
two RecA-like  helicase  domains,  Hel1 and Hel2, and an insert domain, Hel2i)
(see <PDOC51192>),  and  a  C-terminal regulatory (CTR) domain. LGP2 lacks the
two N-terminal  CARDs  but  contains  the  DECH box domain, as well as the CTR
domain. The  CTR  domain  helps  recognize  non-self  RNAs within the cellular
environment. To  facilitate  the  detection  of  a broad range of non-self RNA
targets, each  RLR  contains  a similar but divergent CTR domain that mediates
RLR-specific interactions  between bound nucleic acids or neighboring patterns
[1,2,3,4,5].

The RLR CTR domain is a globular, slightly flattened domain with a concave and
a convex  side  (see <PDB:2W4R>). It is structurally organized in three leaves
consisting of two four-stranded (beta1, beta2, beta9, beta10 and beta5, beta6,
beta7, beta8)  and  one  two-stranded (beta3, beta4) antiparallel beta sheets.
Small helical  turns connect the three beta sheets. The two four stranded beta
sheets are  laterally  connected  by two protruding loops, each containing two
highly conserved  cysteine  residues. Together, the four thiol groups of these
cysteines coordinate a zinc ion [4,5].

The profile we developed covers the entire RLR CTR domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: February 2016 / First entry.

[ 1] Fitzgerald M.E., Rawling D.C., Vela A., Pyle A.M.
     "An evolving arsenal: viral RNA detection by RIG-I-like receptors."
     Curr. Opin. Microbiol. 20:76-81(2014).
     PubMed=24912143; DOI=10.1016/j.mib.2014.05.004
[ 2] Reikine S., Nguyen J.B., Modis Y.
     "Pattern Recognition and Signaling Mechanisms of RIG-I and MDA5."
     Front. Immunol. 5:342-342(2014).
     PubMed=25101084; DOI=10.3389/fimmu.2014.00342
[ 3] Luo D., Ding S.C., Vela A., Kohlway A., Lindenbach B.D., Pyle A.M.
     "Structural insights into RNA recognition by RIG-I."
     Cell 147:409-422(2011).
     PubMed=22000018; DOI=10.1016/j.cell.2011.09.023
[ 4] Cui S., Eisenaecher K., Kirchhofer A., Brzozka K., Lammens A.,
     Lammens K., Fujita T., Conzelmann K.-K., Krug A., Hopfner K.-P.
     "The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of
     RIG-I."
     Mol. Cell 29:169-179(2008).
     PubMed=18243112; DOI=10.1016/j.molcel.2007.10.032
[ 5] Pippig D.A., Hellmuth J.C., Cui S., Kirchhofer A., Lammens K.,
     Lammens A., Schmidt A., Rothenfusser S., Hopfner K.-P.
     "The regulatory domain of the RIG-I family ATPase LGP2 senses
     double-stranded RNA."
     Nucleic Acids Res. 37:2014-2025(2009).
     PubMed=19208642; DOI=10.1093/nar/gkp059

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