Matrix metalloproteinase (MMP) is defined as an endopeptidase in the extracellular matrix (ECM), which plays essential roles in physiological processes such as organogenesis, wound healing, angiogenesis, apoptosis and motility. MMPs are produced and assembled in the cytoplasm as proenzymes with a cytoplasmic domain and require extracellular activation. MMPs can degrade receptors, extracellular matrix proteins, PARPs and release apoptotic substances. MMPs have been found in the cytosol, organelles and extracellular compartments and recently many types of MMPs have been found in the nucleus. However, the mechanisms and roles of MMPs inside the cell nucleus are still poorly understood. Here we summarized the nuclear localization mechanisms of MMPs and their functions in the nucleus such as apoptosis, tissue remodeling upon injury and cancer progression. Most importantly, we found that nuclear MMPs have evolved to translocate to membrane and target ECM possibly through evolution of nuclear localization signal (NLS), natural selection and anti-apoptotic survival. Thus, the knowledge about the evolution and regulation of nuclear MMPs appears to be essential in understanding a variety of cellular processes along with the development of MMP-targeted therapeutic drugs against the progression of certain diseases.

Interferon-inducible transmembrane proteins (IFITM1/2/3) have been reported to suppress the entry of a wide range of viruses. However, their antiviral functional residues and specific mechanisms are still unclear. Here, we firstly resolved the topology of IFITM1 on the plasma membrane where N-terminus points into the cytoplasm and C-terminus resides extracellularly. Further, KRRK basic residues of IFITM1 locating at 62–67 of the conserved intracellular loop (CIL) were found to play a key role in the restriction on the Zika virus (ZIKV) and dengue virus (DENV). Similarly, KRRK basic residues of IFITM2/3 also contributed to suppressing ZIKV replication. Finally, IFITM1 was revealed to be capable of restricting the release of ZIKV particles from endosome to cytosol so as to impede the entry of ZIKV into host cells, which was tightly related with the inhibition of IFITM1 on the acidification of organelles. Overall, our study provided topology, antiviral functional residues and the mechanism of interferon-inducible transmembrane proteins.

A cDNA encoding a new putative serine protease, named Ssmase, was cloned and characterized from the venom gland of the centipede Scolopendra subspinipes mutilans. The cDNA sequence was 1029 bp length, including a 780 bp open reading frame (ORF), a 105 bp 5’ untranslated region, and a 144 bp 3’ untranslated region. The precursor nucleotide sequence of Ssmase was deduced to encode a prepro-peptide of 19 residues and a mature protein of 240 residues. The 19 amino acid residues prepro-peptide of Ssmase putatively composed of 14 amino acids of pre-peptide and 5 amino acids of propeptide (QGSSA). The mature protein of Ssmase contained the typical domain of a trypsin-like serine protease, where His61, Asp108 and Ser208 were the principal residues of the catalytic center. The cysteine residues at 46 to 62, 141 to 214, 180 to 195 and 204 to 233 possibly formed four pairs of disulfide bridges. Ssmase was found to have five N-glycosylation sites (N-Xaa-T/S). To the best of our knowledge, Ssmase was a trypsin-like serine protease firstly characterized from centipede venoms. Ssmase represented a new family of trypsin-like serine protease with four disulfide bridge motif. Key words: Centipede, Scolopendra subspinipes mutilans, trypsin-like serine protease, cysteine motif.