SPRR

SPRR, or Signal Peptide Recognition and Removal, is a crucial process in the biogenesis of secreted and membrane proteins. It occurs in the endoplasmic reticulum (ER) and is mediated by the signal recognition particle (SRP) and the signal peptidase complex. The SPRR process involves several steps:

First, the nascent polypeptide chain, as it emerges from the ribosome, is recognized by the SRP, which is composed of a 7SL RNA and six proteins. The SRP binds to the signal sequence, a short amino-terminal extension of the protein, and targets the ribosome to the ER membrane. Once docked, the SRP is released, and the ribosome translocates the signal sequence into the ER lumen.

After the signal sequence is translocated, the signal peptidase complex, which consists of three subunits (SPP1, SPPL1, and SPPL2), cleaves the signal sequence from the mature protein. This cleavage is essential for the proper folding and secretion of the protein. The signal peptidase complex is anchored in the ER membrane and can cleave the signal sequence at specific sites, typically between alanine and any of the aromatic amino acids (phenylalanine, tyrosine, or tryptophan).

The SPRR process is highly conserved across different species and is essential for the proper functioning of many biological processes. Mutations in genes encoding SPRR components can lead to various diseases, including congenital disorders of glycosylation and other secretory pathway disorders. Understanding the SPRR process is therefore crucial for advancing our knowledge of protein biogenesis and for developing therapeutic strategies for related diseases.