Proline-rich membrane anchor

Hydrophobic-tailed tetramers Abundant form in the mammalian CNS. Anchored to plasma membranes by a hydrophobic, 20 kDalton length polypeptide subunit named PRiMA (Proline-Rich Membrane Anchor). 

Alternative sphcing at the 3 -end of the pre-mRNA yields three different mRNA transcripts (Figure 46.1), which encode proteins with distinct carboxyl termini (Soreq and Seidman, 2001). The synaptic form, AChE-S (also known as T for tailed ), is generated by splicing of exon 4 to exon 6. This is the dominant transcript in most tissues. AChE-S mRNA translation gives rise to a 40 amino acid C-terminal extension of the core AChE. This C-terminal peptide contains cysteine, which allows the formation of dimers and tetramers. These are able to further bind a cholinesterase-specific collagen tail (ColQ) unique to AChE in the NMJ (Massoulie, 2002) or a proline-rich membrane anchor (PRiMA) in the central nervous system (Perrier et al, 2002). Within the NMJ, interactions between the ColQ tails of two or three different tetrameric units and the two structural subunits generate an asymmetric AChE form and anchor it to the synapse (Massoulie, 2002). 

Xie, H.Q., Choi, R.C., Leung, K.W., et al., 2007. Regulation of a transcript encoding the proline-rich membrane anchor of globular muscle acetylcholinesterase. The suppressive roles of myogenesis and innervating nerves. J. Biol. Chem. 282, 11765-11775. 

Fig. 1. Structure and posttranslational processing of PrP. (Upper) Structure of the primary translation product of mammalian PrP. The five proline/glycine-rich repeats in mouse PrP have the sequence P(Q/H)GG(T/G/S)WGQ. (Lower) Structure of the mature protein. The GPI anchor attaches the polypeptide chain to the membrane. (See Fig. 4B for a schematic of the core anchor structure.) Arrows A and B indicate the positions of cleavage sites in PrP, and arrow C a cleavage site in PrP. Site A lies within the GPI anchor, between the glycerolipid moiety and the ethanolamine residue that is attached to the C-terminal amino acid. Site B lies near position HO, and site C near position 89. (Reprinted with permission from Harris, 1999).

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