Biophysical Characterization of SG2NA Variants and their Interaction with DJ-1 and Calmodulin in vitro

Abstract

SG2NA was first discovered as nuclear autoantigen in lung and bladder cancer patient. It was named SG2NA as its expression increases during S to G2 phase of cell cycle. SG2NA/Striatin3 was classified as a member of Striatin family along with Straitin and Zinedin due to its structural and functional relatedness. At the molecular level, SG2NA is characterized by the presence of multiple protein-protein interaction domains viz., a caveolin binding motif, a coiled coil structure, Ca-calmodulin binding domain and a large WD-40 repeat domain in the same order from amino to the carboxyl termini. Analysis of secondary structures of 87 and 78 kDa SG2NA isoforms showed characteristic combinations of α-helix, β-structure, β-turns and random coil; suggesting of effective refolding after denaturation. This study for the first time establishes the structural differences between the two prevalent isoforms of SG2NA. Recently we observed that DJ-1 interacts with variants of SG2NA both in vitro and in vivo. The SG2NA isoforms purified from inclusion bodies showed the different secondary structure conformations, stability and interaction pattern for their interacting partners (DJ-1 and calmodulin) which imparts functional diversity of SG2NA. The SG2NA isoforms showed significant differential binding affinity to DJ-1 and Calmodulin.

High STRN Expression Promotes HCC Invasion and Migration but Not Cell Proliferation or Apoptosis through Facilitating Epithelial-Mesenchymal Transition

“…Members of the striatin family feature multiple protein-binding domains, such as a caveolin-binding motif, a coiled-coil structure, a calmodulin-binding site, and a WD-repeat domain. These domains can mediate the dimerization of members of the striatin family and their interaction with a series of proteins [9]. The STRN-ALK fusion gene, a new driver gene, has been found in multiple cancers, including thyroid cancer [10], non-small-cell lung cancer (NSCLC) [11], colorectal cancer [12], and renal carcinoma [13].…”

Altered expression of striatin‑4 is associated with poor prognosis in bladder transitional cell carcinoma

“…These three proteins manifest in a conservative manner due to their presence both in fungi and higher eukaryotes (5). Numerous studies have reported that the STRN proteins are expressed in various organs such as the central nervous system (6), lung, kidney and testis (7). However, the exact expression pattern differs, which indicates that the STRN family of proteins possess abundant but differential functions at the organ level or cellular level (8).…”