PMID: 22988105

 

    Legend: Gene, Sites

Title : Structural basis for the sheddase function of human meprin β metalloproteinase at the plasma membrane

Abstract :

1. Ectodomain shedding at the cell surface is a major mechanism to regulate the extracellular and circulatory concentration or the activities of signaling proteins at the plasma membrane
2. Human meprin β is a 145-kDa disulfide-linked homodimeric multidomain type-I membrane metallopeptidase that sheds membrane-bound cytokines and growth factors , thereby contributing to inflammatory diseases, angiogenesis, and tumor progression
3. In addition, it cleaves amyloid precursor protein ( APP ) at the β-secretase site , giving rise to amyloidogenic peptides
4. We have solved the X-ray crystal structure of a major fragment of the meprin β ectoprotein , the first of a multidomain oligomeric transmembrane sheddase , and of its zymogen
5. The meprin β dimer displays a compact shape, whose catalytic domain undergoes major rearrangement upon activation, and reveals an exosite and a sugar-rich channel, both of which possibly engage in substrate binding
6. A plausible structure-derived working mechanism suggests that substrates such as APP are shed close to the plasma membrane surface following an "N-like" chain trace

Output (sent_index, trigger, protein, sugar, site):

Output(Part-Of) (sent_index, protein, site):

• 4. ectoprotein, fragment
• 4. sheddase, fragment

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
meprin β	4225	0,4,5
Human meprin β	4225	2
amyloid precursor protein	351	3