Group:MUZIC:ALP

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== Structures ==
== Structures ==
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Molecular structures of the PDZ and/or LIM domains of [http://www.pdb.org/pdb/explore/explore.do?structureId=2PKT PDLIM1 (hCLIM1/CLP36)], [http://www.pdb.org/pdb/results/results.do?qrid=185C6F4B&tabtoshow=Current PDLIM2 (Mystique)], [http://www.pdb.org/pdb/results/results.do?qrid=EDAB5DC2&tabtoshow=Current PDLIM3 (ALP)] and [http://www.pdb.org/pdb/results/results.do?qrid=D3075EE4&tabtoshow=Current PDLIM4 (RIL)] have been solved, in thier apo form, and in complex with the C-terminal extension of their binding partners. These structures present insightful features highlighting their respective interactions and functions.
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Molecular structures of the PDZ and/or LIM domains of [http://www.pdb.org/pdb/explore/explore.do?structureId=2PKT PDLIM1 (hCLIM1/CLP36)], [http://www.pdb.org/pdb/results/results.do?qrid=185C6F4B&tabtoshow=Current PDLIM2 (Mystique)], [http://www.pdb.org/pdb/results/results.do?qrid=EDAB5DC2&tabtoshow=Current PDLIM3 (ALP)] and [http://www.pdb.org/pdb/results/results.do?qrid=D3075EE4&tabtoshow=Current PDLIM4 (RIL)] have been solved, in their apo form, and in complex with the C-terminal extension of their binding partners. These structures present insightful features highlighting their respective interactions and functions.
==Function and Interactions==
==Function and Interactions==

Revision as of 21:33, 12 January 2013

Contents

Introduction

The ALP subfamily (α-Actinin-associated LIM domain Proteins) comprises four PDZ/LIM domain proteins of the cytoskeleton. Protein members of this subfamily include: ALP (also known as PDLIM3)[1], CLP36 (also known as hCLIM1 (in human)[2], Elfin (in mouse)[3], or PDLIM1), RIL (or PDLIM4) and Mystique (or SLIM, PDLIM2)[4][5]. On the basis of structural similarities, the ALP subfamily are related to the Enigma subfamily, possessing PDZ and LIM domains, as well as internal motifs viz ALP-like motif (AM) and ZASP-like motif (ZM). However, the ALP subfamily differs from the Enigma subfamily as each member of the ALP subfamily possess an N-terminal PDZ domain and only one C-terminal LIM domain.

CLP36 (C-terminal LIM Protein 36 kDa)[6] and RIL (Reversion-Induced LIM)[7] were the first protein members to be characterised in this subfamily. α-Actinin-associated LIM protein (ALP) was later identified as a 39 kDa protein in rat skeletal muscle with a slightly shorter isoform in heart [1], which shares a high degree of homology with the first protein members of the subfamily - CLP36 and RIL [8]. Mystique is the most recently identified and characterised member of the ALP subfamily.

Sequence annotation

Domain map in the first isoforms of human ALP subfamily members: ALP [1] Mystique [2] RIL [3] hCLIM1[4]
Domain map in the first isoforms of human ALP subfamily members: ALP [1] Mystique [2] RIL [3] hCLIM1[4]

Apart from the PDZ/LIM domains, ALP subfamily members possess a conserved 34-amino-acid motif called ALP-like motif [9]

ALP (PDLIM3: PDZ and LIM domain protein 3) is the 39 kDa, 364 amino-acid protein present in heart and skeletal muscle with three splice isoforms presently identified UniProtKB ID: Q53GG5 [5]. Apart from the PDZ domain, ALP carries two internal motifs (ZASP-like motif) and (ALP-like motif) which confers the ability to interact with α-actinin-2.

Mystique, identified in human and also referred to as PDLIM2, is the most recent member of the family with ~37.5 kDa, 352 amino-acid[10]. Four alternatively spliced isoforms have been described (UniProtKB ID:Q96JY6)[6].

RIL protein, alternatively referred to as PDLIM4, is the smallest at ~35.4 kDa of the ALP subfamily. Initially characterized in rat, it is well conserved in diverse species with 330 amino acids. Two alternatively spliced isoforms are presently identified (UniProtKB ID: P50479)[7].

hCLIM1 also referred to as PDLIM1, is the human orthologue of rat CLP36, the first member of the ALP subfamily. At 36 kDa and 329 amino acids, splice isoform of this protein is yet unidentified (UniProtKB ID:O00151 [8].

Structures

Molecular structures of the PDZ and/or LIM domains of PDLIM1 (hCLIM1/CLP36), PDLIM2 (Mystique), PDLIM3 (ALP) and PDLIM4 (RIL) have been solved, in their apo form, and in complex with the C-terminal extension of their binding partners. These structures present insightful features highlighting their respective interactions and functions.

Function and Interactions

All member proteins of ALP subfamily have been shown to interact with component proteins of the cytoskeleton, particularly α-actinin-2 at the Z-disk; an elegant summary of the molecular interactions and plausible functions of ALP, Mystique, RIL, and hCLIM1 can be found in [11] and [12].

Pathology

Deficiency in cardiac development and cardiac malfunction resulting from mutation and genetic studies have been indentified within the ALP subfamily [13] and [14].

References

  1. ↑ 1.0 1.1 Xia H, Winokur ST, Kuo WL, Altherr MR, Bredt DS. Actinin-associated LIM protein: identification of a domain interaction between PDZ and spectrin-like repeat motifs. J Cell Biol. 1997 Oct 20;139(2):507-15. PMID:9334352
  2. ↑ Kotaka M, Ngai SM, Garcia-Barcelo M, Tsui SK, Fung KP, Lee CY, Waye MM. Characterization of the human 36-kDa carboxyl terminal LIM domain protein (hCLIM1). J Cell Biochem. 1999 Feb 1;72(2):279-85. PMID:10022510
  3. ↑ Kotaka M, Lau YM, Cheung KK, Lee SM, Li HY, Chan WY, Fung KP, Lee CY, Waye MM, Tsui SK. Elfin is expressed during early heart development. J Cell Biochem. 2001 Aug 21-Sep 5;83(3):463-72. PMID:11596114
  4. ↑ Torrado M, Senatorov VV, Trivedi R, Fariss RN, Tomarev SI. Pdlim2, a novel PDZ-LIM domain protein, interacts with alpha-actinins and filamin A. Invest Ophthalmol Vis Sci. 2004 Nov;45(11):3955-63. PMID:15505042 doi:10.1167/iovs.04-0721
  5. ↑ Loughran G, Healy NC, Kiely PA, Huigsloot M, Kedersha NL, O'Connor R. Mystique is a new insulin-like growth factor-I-regulated PDZ-LIM domain protein that promotes cell attachment and migration and suppresses Anchorage-independent growth. Mol Biol Cell. 2005 Apr;16(4):1811-22. Epub 2005 Jan 19. PMID:15659642 doi:10.1091/mbc.E04-12-1052
  6. ↑ Wang H, Harrison-Shostak DC, Lemasters JJ, Herman B. Cloning of a rat cDNA encoding a novel LIM domain protein with high homology to rat RIL. Gene. 1995 Nov 20;165(2):267-71. PMID:8522188
  7. ↑ Kiess M, Scharm B, Aguzzi A, Hajnal A, Klemenz R, Schwarte-Waldhoff I, Schafer R. Expression of ril, a novel LIM domain gene, is down-regulated in Hras-transformed cells and restored in phenotypic revertants. Oncogene. 1995 Jan 5;10(1):61-8. PMID:7824279
  8. ↑ 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
  9. ↑ te Velthuis AJ, Bagowski CP. PDZ and LIM domain-encoding genes: molecular interactions and their role in development. ScientificWorldJournal. 2007 Sep 1;7:1470-92. PMID:17767364 doi:10.1100/tsw.2007.232
  10. ↑ Ueki N, Seki N, Yano K, Masuho Y, Saito T, Muramatsu M. Isolation, tissue expression, and chromosomal assignment of a human LIM protein gene, showing homology to rat enigma homologue (ENH). J Hum Genet. 1999;44(4):256-60. PMID:10429367 doi:10.1007/s100380050155
  11. ↑ te Velthuis AJ, Bagowski CP. PDZ and LIM domain-encoding genes: molecular interactions and their role in development. ScientificWorldJournal. 2007 Sep 1;7:1470-92. PMID:17767364 doi:10.1100/tsw.2007.232
  12. ↑ 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
  13. ↑ te Velthuis AJ, Bagowski CP. PDZ and LIM domain-encoding genes: molecular interactions and their role in development. ScientificWorldJournal. 2007 Sep 1;7:1470-92. PMID:17767364 doi:10.1100/tsw.2007.232
  14. ↑ 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
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