Intrinsic disorder in spondins and some of their interacting partners

Abstract

Spondins, which are proteins that inhibit and promote adherence of embryonic cells so as to aid axonal growth are part of the thrombospondin-1 family. Spondins function in several important biological processes, such as apoptosis, angiogenesis, etc. Spondins constitute a thrombospondin subfamily that includes F-spondin, a protein that interacts with Ab precursor protein and inhibits its proteolytic processing; R-spondin, a 4-membered group of proteins that regulates Wnt pathway and have other functions, such as regulation of kidney proliferation, induction of epithelial proliferation, the tumor suppressant action; M-spondin that mediates mechanical linkage between the muscles and apodemes; and the SCO-spondin, a protein important for neuronal development. In this study, we investigated intrinsic disorder status of human spondins and their interacting partners, such as members of the LRP family, LGR family, Frizzled family, and several other binding partners in order to establish the existence and importance of disordered regions in spondins and their interacting partners by conducting a detailed analysis of their sequences, finding disordered regions, and establishing a correlation between their structure and biological functions.

Proteomic analysis of heart failure hospitalization among patients with chronic kidney disease: The Heart and Soul Study

“…[44] High concentrations of F-spondin are found in the human ovary, where it is known to stimulate vascular smooth muscle cell proliferation. [45] Given the negative Spearman correlation of Spondin-1 with eGFR and albuminuria, it follows that Spondin-1 levels were lower in those with higher eGFR, yet the Spondin-1-HF association was significantly stronger in these non-CKD patients. This could be due to a saturation point of Spondin-1 or its effectors, and warrants further study.…”

Alteration of Wnt5a expression and of the non-canonical Wnt/PCP and Wnt/PKC-Ca2+ pathways in human osteoarthritis osteoblasts

“…Also, both with p -JNK and p -PKC, the addition of Rspo-2 in conjunction with Wnt5a, but not alone, was able to boost the effect of Wnt5a supporting the idea that Rspo-2 is crucial to further stimulate the non-canonical pathways. Indeed, Rspo-2 on its own cannot stimulate the Wnt non-canonical pathways yet it promotes the effect of non-canonical Wnts on these pathways via LGRs [ 55 – 57 ]. Further, we were able to demonstrate that Wnt5a alone cannot stimulate the canonical Wnt/β-catenin signaling pathway in OA Ob whereas it also does not inhibit nor increase the stimulation observed in response to Wnt3a alone.…”

Configurational Entropy of Folded Proteins and Its Importance for Intrinsically Disordered Proteins

“…We carry this idea further to predict that the force fields with ~ for folded proteins will be better suited to representing the structural ensembles of IDRs and IDPs as well; by corollary, force fields with < for folded states will not be able to describe the greater plasticity of intrinsically disordered states. To test the extrapolation from folded proteins, we now consider the TSR4 domain (1vex), which comprises a small β-sheet core stabilized by a network of pi-contacts, with large loops that have been classified as intrinsically disordered regions [ 59 ]. For TSR4 (1vex), the <RMSD> values for all force fields ( Table 2 ) are well outside the metric (1.34 Å) and in better agreement with the value (4.49 Å) given the presence of significant segments of disorder.…”