Group:MUZIC:MLP: Difference between revisions
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== Cystein and glycine-rich protein 3 (CSRP3) == | === Cystein and glycine-rich protein 3 (CSRP3) === | ||
== Introduction == | == Introduction == | ||
The '''Cystein and glycine-rich protein 3 (CSRP3 | The '''Cystein and glycine-rich protein 3''' ('''CSRP3'''), or as also known as '''Muscle LIM Protein''' ('''MLP'''), '''Cardiac LIM protein''', or '''Cysteine-rich protein 3''' ('''CRP3'''), is one of the three CSRP family members identified in vertebrates. CSRP3 has been identified muscle and cardiac cells<ref name="r1">PMID: 7490106</ref>. The three family members contain 192-194 residues and two [[LIM]] domains adjacent to a flexible glycine-rich linker. Each LIM domain comprises two Zn-binding motifs CCHC and CCCC representing a structural and presumably functional independent unit. | ||
== Sequence Annotation == | == Sequence Annotation == | ||
CSRP3 comprises 194 | CSRP3 comprises 194 amino acids with two 52 residue [[LIM]] domains. Each of them is followed by glycine-rich sequences of about 10-20 residues [http://www.uniprot.org/uniprot/P50461 UNIPROT (CSRP3_HUMAN)]. | ||
== Structures == | == Structures == | ||
LIM domains have been intensively characterized using NMR. The | <StructureSection load='2o13' size='250' frame='true' align='right' caption='Solution structure of the C-terminal LIM domain of MLP/CSRP3 (PDB entry: [http://www.pdb.org/pdb/explore/explore.do?structureId=2o13 2o13 ]), Colour code: blue: N-term, red: C-term' scene='Group:MUZIC:MLP/Ctermlim/1' /> | ||
<StructureSection load='2o10' size='250' frame='true' align='right' caption='Solution structure of the N-terminal LIM domain of MLP/CSRP3 (PDB entry: [http://www.pdb.org/pdb/explore/explore.do?structureId=2O10 2o10 ]), Colour code: blue: N-term, red: C-term' scene='Group:MUZIC:MLP/Lim1/1' /> | |||
[[LIM]] domains have been intensively characterized using NMR. The two [[LIM]] domains of CSRP3 have been determined by NMR ([http://www.pdb.org/pdb/explore/explore.do?structureId=2O10 LIM1: 2O10 ] and [http://www.pdb.org/pdb/explore/explore.do?structureId=2O13 LIM2: 2O13 ]) | |||
== Function and Interactions == | == Function and Interactions == | ||
All three | All three CSRPs are associated with the actin cytoskeleton and have similar functions in different muscle types. They up-regulate the myogenesis and have specific roles in the organisation of cytosolic structures in cardiomyocytes. It was also suggested that CSRPs may have a role in stretch sensing<ref name="r2">PMID: 12507422</ref>. MLP (CSRP3) is localized mainly in the Z-disc and the M-band of the striated muscle<ref>PMID:10751147</ref>. Within the Z-disc, the interactions of CSRP3 with [http://www.proteopedia.org/wiki/index.php/Group:MUZIC:Telethonin telethonin] and α-actinin2 have been reported previously<ref name="r2">PMID: 12507422</ref><ref>PMID: 16407954</ref><ref>PMID: 9341203</ref>, a more recent report however underscoring the role of CSRP3 as a scaffold protein<ref name="r3">PMID:18505755</ref>. CSRP3 has also been suggested to interact with βI-spectrin, N-RAP (Nebulin-related-anchoring protein) and cofilin2 (CFL2), underlying the essential role of CSRP3 as a scaffold protein. During myofibrilogenesis CSRP3 has been proposed to form complexes with the muscle helix-loop-helix transcription factors MyoD, MRF4 and myogenin <ref name="r3">PMID:18505755</ref>. Finally, it is involved in the anchorage of calcineurin to the Z-disc<ref>PMID: 15665106</ref>. | ||
== Pathology == | == Pathology == | ||
CSRP3(MLP) has been inmplicated in two types of hereditary cardiomyopathies, hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). | |||
Familial HCM is a hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death <ref>PMID:12642359</ref>. Mutations in the first LIM domain have been linked to HCM and allll of them ('''L44P, S54R, E55G, C58G''') are related to the proper binding of Zinc to the protein, thus causing conformational alterations. | |||
Dilated cardiomyopathy (DCM) is a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia and patients have the risk of premature death <ref name="r2">PMID:12507422</ref>. The mutation '''W4R''' in CSRP3 has been reported to cause dilated cardiomyopathy (DCM) of type 1Mv. However in more recent reports there is the suggestion that this allelic variant might actually be a common polymorphism <ref name="r3">PMID:18505755</ref><ref> PMID: 17084280</ref>. | |||
== References == | == References == | ||
<references /> | <references /> | ||