Eichler Robert, Lenz Oliver, Strecker Thomas, Garten Wolfgang
Institut für Virologie der Philipps-Universität Marburg, Robert-Koch-Strasse 17, D-35037 Marburg, Germany.
FEBS Lett. 2003 Mar 13;538(1-3):203-6. doi: 10.1016/s0014-5793(03)00160-1.
Lassa virus glycoprotein is synthesized as precursor GP-C into the lumen of the endoplasmic reticulum and cleaved posttranslationally into the N-terminal subunit GP-1 and the C-terminal subunit GP-2 by subtilase SKI-1/S1P. The N-terminal portion of the primary translation product preGP-C contains a signal peptide of unknown length. In order to demonstrate the signal peptide cleavage site, purified viral GP-1 isolated from Lassa virus particles was N-terminally sequenced as TSLYKGV, identical to amino acids 59-65 of GP-C. Mutational analysis of the amino acid residues flanking the putative cleavage site led to non-cleavable preGP-C indicating that no other signal peptide cleavage site exists. Interestingly, GP-C mutants with a non-cleavable signal peptide were not further processed by SKI-1/S1P. This observation suggests that the signal peptide cleavage is necessary for GP-C maturation and hence for Lassa virus replication.
拉沙病毒糖蛋白以内质网腔中的前体GP-C形式合成，并在翻译后被枯草杆菌蛋白酶SKI-1/S1P切割成N端亚基GP-1和C端亚基GP-2。初级翻译产物preGP-C的N端部分包含一个长度未知的信号肽。为了证明信号肽切割位点，从拉沙病毒颗粒中分离出的纯化病毒GP-1进行N端测序，结果为TSLYKGV，与GP-C的第59至65位氨基酸相同。对假定切割位点两侧氨基酸残基的突变分析导致preGP-C不可切割，表明不存在其他信号肽切割位点。有趣的是，具有不可切割信号肽的GP-C突变体不会被SKI-1/S1P进一步加工。这一观察结果表明，信号肽切割对于GP-C成熟以及拉沙病毒复制是必需的。
