Prelamin-A
Description
Prelamin-A is a structural component of the nuclear lamina and it is encoded by lamin A/C gene (LMNA). Due to the presence of a CAAX box sequence at carboxyl terminus, Prelamin-A in vivo goes through a serial of post-translational modifications, resulting in the farnesylation of the cysteine thiol, removal of the AAX tripeptide, carboxyl-methylation of the cysteinyl carboxy group and proteolysis of 18 C-terminal amino acids residues that lead to mature lamin A. Diverse mutations in the lamin A/C gene are associated with different deseases that are collectively called laminophaties, including Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. Recombinant human prelamin A is fused to a 6 Histidine tag at the N-terminus.
Product Specs
HHHHHH-METPSQRRATRSGAQASSTPLSPTRITRLQEKEDLQELNDRLAVYIDRVHSLETENAGLRLRITES
EEVVSREVSGIKAAYEAELGDARKTLDSVAKERARLQLELSKVREEFKELKARNTKKEGDLIAAQA
RLKDLEALLNSKEAALSTALSEKRTLEGELHDLRGQVAKLEAALGEAKKQLQDEMLRRVDAENRL
QTMKEELDFQKNIYSEELRETKRRHETRLVEIDNGKQREFESRLADALQELRAQHEDQVEQYKKE
LEKTYSAKLDNARQSAERNSNLVGAAHEELQQSRIRIDSLSAQLSQLQKQLAAKEAKLRDLEDSLA
RERDTSRRLLAEKEREMAEMRARMQQQLDEYQELLDIKLALDMEIHAYRKLLEGEEERLRLSPSP
TSQRSRGRASSHSSQTQGGGSVTKKRKLESTESRSSFSQHARTSGRVAVEEVDEEGKFVRLRN
KSNEDQSMGNWQIKRQNGDDPLLTYRFPPKFTLKAGQVVTIWAAGAGATHSPPTDLVWKAQNT
WGCGNSLRTALINSTGEEVAMRKLVRSVTVVEDDEDEDGDDLLHHHHGSHCSSSGDPAEYNLRS
RTVLCGTCGQPADKASASGSGAQVGGPISSGSSASSVTVTRSYRSVGGSGGGSFGDNLVTRSYL
LGNSSPRTQSPQNCSIM
Product Science Overview
Prelamin A undergoes a series of modifications at its C-terminal end:
- Farnesylation: Addition of a farnesyl group to the cysteine residue within the CaaX motif (C: cysteine; a: aliphatic; X: any residue).
- Endoproteolytic Cleavage: Removal of the last three amino acids of the CaaX motif by the enzyme ZMPSTE24.
- Carboxymethylation: Addition of a methyl group to the newly exposed carboxyl group of the cysteine residue.
- Second Endoproteolytic Cleavage: Removal of the farnesylated cysteine residue by ZMPSTE24 .
Interestingly, recent studies have shown that the sequence of these events might differ from the accepted dogma. For instance, the upstream SY^LL cleavage occurs before and independently of the C-terminal CSIM modifications .
Mutations in the LMNA gene, which encodes lamin A and C, can lead to a variety of diseases known as laminopathies. These include:
- Hutchinson-Gilford Progeria Syndrome (HGPS): A rare disorder that mimics premature aging. It is caused by a mutation that leads to the accumulation of a farnesylated form of prelamin A, known as progerin .
- Mandibuloacral Dysplasia (MAD): Characterized by skeletal abnormalities and lipodystrophy .
- Familial Partial Lipodystrophy: Affects adipose tissue distribution .
Recombinant prelamin-A is produced using genetic engineering techniques to study its structure, function, and processing. This involves expressing the prelamin-A gene in a host system, such as bacteria or insect cells, and purifying the protein for further analysis . Studies using recombinant prelamin-A have provided valuable insights into the mechanisms of its processing and the effects of mutations.
