ICA512 RESP18 homology domain is a protein-condensing factor and insulin fibrillation inhibitor.

ABSTRACT: Type 1 diabetes islet cell autoantigen 512 (ICA512/IA-2) is a tyrosine phosphatase-like intrinsic membrane protein involved in the biogenesis and turnover of insulin secretory granules (SGs) in pancreatic islet β-cells. Whereas its membrane-proximal and cytoplasmic domains have been functionally and structurally characterized, the role of the ICA512 N-terminal segment named "regulated endocrine-specific protein 18 homology domain" (RESP18HD), which encompasses residues 35-131, remains largely unknown. Here, we show that ICA512 RESP18HD residues 91-131 encode for an intrinsically disordered region (IDR), which in vitro acts as a condensing factor for the reversible aggregation of insulin and other β-cell proteins in a pH and Zn²⁺-regulated fashion. At variance with what ha

SUBMITTER: Toledo PL 

PROVIDER: S-EPMC6544868 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature