Biology subjects

Tellgren-Roth, A.

Publications and source records attributed to Tellgren-Roth, A..

2 recordsLinked to original sources

bioRxiv2019

Membrane integration and topology of RIFIN and STEVOR proteins of the Plasmodium falciparum parasite

The malarial parasite Plasmodium, infects red blood cells by remodeling them and transporting its own proteins to their cell surface. These proteins trigger adhesion of infected cells to uninfected cells (rosetting), and to the vascular endothelium, obstructing blood flow and contributing to pathogenesis. RIFINs (P. falciparum-encoded repetitive interspersed families of polypeptides) and STEVORs (subtelomeric variable open reading frame), are two classes of proteins that are involved in rosetting. Here we study the membrane insertion and topology of three RIFIN and two STEVOR proteins, employing a well-established assay that uses N-linked glycosylation of sites within the protein as a measure to assess the topology a protein adopts when inserted into the ER membrane. Our results indicate that all the proteins tested assume an overall topology of Ncyt-Ccyt, with predicted transmembrane helices TM1 and TM3 integrated into the ER membrane. We also show that the segments predicted as TM2 do not reside in the membrane. Our conclusions are consistent with other recent topology studies on RIFIN and STEVOR proteins.

biochemistry↗

bioRxiv2018

Astrotactins 1 and 2 have similar membrane topology and mature via endoproteolytic cleavage catalyzed by signal peptidase

Astrotactins 1 and 2 (Astn1, Astn2) are membrane proteins that function in glial-guided migration, receptor trafficking and synaptic plasticity in brain, as well as in planar polarity pathways in skin. Here, we have mapped the topologies of mouse Astn1 and Astn2 in rough microsomal membranes (RMs) using glycosylation mapping and protease-protection assays, and find that Astn2 has a cleaved N-terminal signal peptide (SP), an N-terminal domain located in the lumen of the RMs (topologically equivalent to the extracellular surface in cells), two transmembrane helices (TMHs), and a large C-terminal lumenal domain. We find that Astn1 has the same topology as Astn2 but see no evidence of SP cleavage. Both Astn1 and Astn2 mature through endoproteolytic cleavage in the second TMH; importantly, we identify the endoprotease responsible for the maturation of Astn1 and Astn2 as signal peptidase. Differences in the degree of the maturation of Astn1 and Astn2 possibly contribute to the higher levels of the C-terminal domain of Astn1 detected on the CNS neuronal membranes and to the different functions of Astn1 and Astn2.

neuroscience↗