Group:MUZIC:Enigma Family

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Enigma family: PDZ- and LIM-domain protein of the cytoskeleton

Three proteins have extensively been described and characterized within this subfamily: Enigma, Enigma Homologue (ENH) protein and ZASP/Cypher ('ZASP'[1] being the human orthologue of 'Cypher'[2] which is found in mouse and also identified by independent researchers who named it 'Oracle'[3]).

Didactically, protein members of the enigma subfamily typically possess within their structure: (1) an N-terminal PDZ domain (a domain which is named after the first three proteins where it was initially characterized i.e. PSD 95, Disc large protein and Zonula Occludens 1), and (2) three C-terminal LIM domain (a domain which is named after the first three proteins where it was characterized i.e. Lin-11, Isl1 and Mec-3)[4].

The member proteins have all been located to the mammalian striated muscle, specifically in the heart and skeletal muscle Z-disk. They interact via their PDZ domains with motor protein components of the Z-disk and also recruit signalling molecules via thier LIM domain or internal motifs, for example ZM motif (ZASP-like motif which is sandwiched between the PDZ- and LIM-domains in ZASP)[5].

These interactions via their PDZ- and LIM-domains have been suggested to be important for targeting and maintaining protein complexes in the sarcomere in order to maintain a proper architecture and physiologically functional muscle.

NMR structure of the PDZ domain of ENH protein

Drag the structure with the mouse to rotate

Enigma

Structure

Interactions within the Z-disk

Functions


Enigma Homologue (ENH) protein

Structure

Interaction within the Z-disk

Functions


ZASP/Cypher/Oracle

Structure

Interactions within the Z-disk

Functions



References

  1. ↑ Faulkner G, Pallavicini A, Formentin E, Comelli A, Ievolella C, Trevisan S, Bortoletto G, Scannapieco P, Salamon M, Mouly V, Valle G, Lanfranchi G. ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol. 1999 Jul 26;146(2):465-75. PMID:10427098
  2. ↑ Zhou Q, Ruiz-Lozano P, Martone ME, Chen J. Cypher, a striated muscle-restricted PDZ and LIM domain-containing protein, binds to alpha-actinin-2 and protein kinase C. J Biol Chem. 1999 Jul 9;274(28):19807-13. PMID:10391924
  3. ↑ Passier R, Richardson JA, Olson EN. Oracle, a novel PDZ-LIM domain protein expressed in heart and skeletal muscle. Mech Dev. 2000 Apr;92(2):277-84. PMID:10727866
  4. ↑ Zheng M, Cheng H, Banerjee I, Chen J. ALP/Enigma PDZ-LIM domain proteins in the heart. J Mol Cell Biol. 2010 Apr;2(2):96-102. Epub 2009 Dec 30. PMID:20042479 doi:10.1093/jmcb/mjp038
  5. ↑ Wang X, Su H. Unraveling enigma in the z-disks. Circ Res. 2010 Aug 6;107(3):321-3. PMID:20689070 doi:10.1161/CIRCRESAHA.110.225615

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