ABCD3 Membrane Protein Introduction

Introduction of ABCD3

ABCD3, also known as PXMP1, ABC43, CBAS5, ZWS2, peroxisomal membrane protein-1, peroxisomal membrane protein 1 (70 kDa, Zellweger syndrome), or DJ824O18.1 (ATP-binding cassette, sub-family D (ALD), member 3), is a 75.5 kDa transport protein that consists of 659 amino acids. In humans, it is encoded by the ABCD3 gene which is localized at the chromosome 1p21.3. ABCD3 is one of the peroxisomal ATP-binding Cassette (ABC) transporters and in mammalian, there are four peroxisomal ABC proteins have been confirmed in mammalian peroxisomes, including adrenoleukodystrophy protein (ALDP, ABCD1), ALDP-related protein (ALDRP, ABCD2), 70-kDa peroxisomal membrane protein (PMP70, ABCD3), and PMP70-related protein (P70R, ABCD4). They are all transmembrane proteins involved in the transport of numerous lipids allowing their degradation inside the organelle.

Function of ABCD3 Membrane Protein

ABCD3 is a member of the ATP-binding cassette, sub-family D (ALD) subfamily, which participates in the peroxisomal import of fatty acids and fatty acyl-CoAs in organelles. And it is reported that ABCD3 is implicated in the transport of long and branched chain acyl-CoA. It is well-known that peroxisomal ABC transporters are half transporters requiring a partner of half transporter molecule to constitute a functional homodimeric or heterodimeric transporter. Like other half-size ABC proteins, ABCD3 is thought to work after dimerization and this peroxisomal membrane protein may play an essential role in peroxisome biogenesis. Mutations of ABCD3 gene have been correlated with the formation of Zellweger syndrome, a heterogeneous disease of peroxisome assembly disorders. Another disease correlated with ABCD3 deficiencies is known as bile acid synthesis defect, congenital. Its associated pathways contain the removal of Cdc6 and peroxisome as well as the CDK-mediated phosphorylation. An important paralog of ABCD3 is the ABCD2 gene. Moreover, ABCD3 has been demonstrated to interact with PEX19, a protein necessary for the early peroxisomal biogenesis.

Fig.1 Hypothesized structure of the peroxisomal ABC half-transporter. (Morita, 2012)

Application of ABCD3 Membrane Protein in Literature

1. Mayer L., et al. ABCD3-I score and the risk of early or 3-month stroke recurrence in tissue- and time-based definitions of TIA and minor stroke. J Neurol. 2018, 265(3): 530-534. PubMed ID: 29327286
   
   

   This report changed the definition of TIA from time to a tissue basis, which questioned the validity of well-established ABCD3-I risk score for recurrent ischemic cerebrovascular cases. Authors analyzed patients with this disease-carrying mild neurological symptoms not up to 24 h after symptom onset in a phase.

2. Zhao M., et al. Comparison of stroke prediction accuracy of ABCD2 and ABCD3-I in patients with transient ischemic attack: a meta-analysis. J Stroke Cerebrovasc Dis. 2017, 26(10): 2387-2395. PubMed ID: 28647418
   
   

   The ABCD3-I score had a better sensitivity but poorer specificity compared to the ABCD2 score. In community-based referring settings, ABCD2 was more suitable to be used at the initial triage. During clinical triage, the prognostic utility of each component of scores should be considered carefully.

3. Debbabi M., et al. Flow cytometric analysis of the expression pattern of peroxisomal proteins, Abcd1, Abcd2, and Abcd3 in BV-2 murine microglial cells. Methods Mol Biol. 2017, 1595: 257-265. PubMed ID: 28409470
   
   

   This review evaluated the expression pattern of various peroxisomal transporters, including Abcd1, Abcd2, Abcd3, which contributed to the peroxisomal β-oxidation on BV-2 cells by flow cytometry (FCM) and other complementary methods (RT-qPCR and fluorescence microscopy). By FXM, a strong expression of these three peroxisomal proteins was observed.

4. Andreoletti P., et al. Predictive structure and topology of peroxisomal ATP-binding cassette (ABC) transporters. Int J Mol Sci. 2017, 18(7). PubMed ID: 28737695
   
   

   According to the crystal structure of mitochondrial ATP-binding cassette (ABC) transporter ABCB10, scientists proposed a model of peroxisomal ABCD proteins that specified the position of transmembrane and coupling helices and emphasized functional motifs and putative essential amino acid residues.

5. Knoflach M., et al. Predictive value of ABCD2 and ABCD3-I scores in TIA and minor stroke in the stroke unit setting. Neurology. 2016, 87(9): 861-869. PubMed ID: 27473138
   
   

   Standard ABCD2 and ABCD3-I scores were beneficial instruments to assess the possibility of early and three-month stroke in TIA as well as minor stroke patients treated at specific stroke units, with C, D, and I being the most significant score constituted in this setting.

ABCD3 Preparation Options

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Reference

1. Morita M and Imanaka T. (2012). Peroxisomal ABC transporters: structure, function and role in disease. Biochim Biophys Acta. 1822(9): 1387-1396.

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