Rancaño C, Rubio T, Correas I, Alonso M A
Centro de Biología Molecular, Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Spain.
J Biol Chem. 1994 Mar 18;269(11):8159-64.
Genomic DNA clones containing the T-cell-specific human MAL gene were isolated. Restriction and sequence analysis revealed four exons and three introns. Each hydrophobic segment of MAL together with its adjacent hydrophilic sequence correlates closely with one exon of the gene. RNase protection analysis revealed that the previously described MAL mRNA, which contains the sequences present in the four exons, is the mRNA species predominant in T-cells. A remarkable similarity was found between the hydrophobicity pattern of MAL and those of the peripheral membrane protein 22 (PMP-22) and the 16-kDa proteolipid of vacuolar H(+)-ATPase. Direct evidence supporting that MAL is a proteolipid was obtained by extracting bacterial lysates expressing recombinant MAL protein with lipophilic solvents used to extract lipids. The use of two different antibodies raised against distinct peptides from the MAL molecule has allowed the localization of MAL in the endoplasmic reticulum of T-cells. This subcellular localization is in agreement with the presence of a RWKSS motif in the COOH-terminal tail of MAL, next to its last putative transmembrane domain, that fits with one of the consensus sequences (RXKXX) for residency in the endoplasmic reticulum for transmembrane proteins. A possible function for MAL protein in T-cells is discussed based on its subcellular localization and the unique lipid-like properties of the proteolipid proteins.
