Cartilage acidic protein 1, a new member of the beta-propeller protein family with amyloid propensity

Abstract

Cartilage acidic protein1 (CRTAC1) is an extracellular matrix protein of chondrogenic tissue in humans and its presence in bacteria indicate it is of ancient origin. Structural modeling of piscine CRTAC1 reveals it belongs to the large family of beta-propeller proteins that in mammals have been associated with diseases, including amyloid diseases such as Alzheimer's. In order to characterize the structure/function evolution of this new member of the beta-propeller family we exploited the unique characteristics of piscine duplicate genes Crtac1a and Crtac1b and compared their structural and biochemical modifications with human recombinant CRTAC1. We demonstrate that CRTAC1 has a beta-propeller structure that has been conserved during evolution and easily forms high molecular weight thermo-stable aggregates. We reveal for the first time the propensity of CRTAC1 to form amyloid-like structures, and hypothesize that the aggregating property of CRTAC1 may be related to its disease-association. We further contribute to the general understating of CRTAC1's and beta-propeller family evolution and function. Proteins 2017; 85:242-255. © 2016 Wiley Periodicals, Inc.

Network Analysis Reveals Putative Genes Affecting Meat Quality in Angus Cattle

“…KLHL2 is a component of an ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, which most often leads to their proteasomal degradation and plays a role in the actin cytoskeleton reorganization. The CRTAC1 gene encodes a glycosylated extracellular matrix protein located in the interterritorial matrix of articular deep zone cartilage and the protein may be involved in cell-cell or cell-matrix interactions (Anjos et al, 2017 ). Overall, these examples provide strong evidence that the network methodology used in this study allows the co-localization of biologically relevant genes with a close relationship to different aspects of meat quality variation.…”

Keratan sulfate (KS)‐proteoglycans and neuronal regulation in health and disease: the importance ofKS‐glycodynamics and interactive capability with neuroregulatory ligands

“…; Anjos et al . ). CRATC1 is a chondrocyte marker protein which has been used to differentiate cells with a chondroprogenitor and osteoprogenitor background (Grgurevic et al .…”

“…Cartilage acidic protein 1B (CRTAC1-B, LOTUS) is an alternatively spliced form of cartilage acidic protein-1 (CRTAC1) which is expressed exclusively in the CNS. CRTAC1 is a chondrocyte ECM protein member of a large family of evolutionary and phylogenetically conserved beta-propellor proteins (Redruello et al 2010;Anjos et al 2017). CRATC1 is a chondrocyte marker protein which has been used to differentiate cells with a chondroprogenitor and osteoprogenitor background (Grgurevic et al 2007;Steck et al 2007).…”

Cartilage acidic protein 1 promotes increased cell viability, cell proliferation and energy metabolism in primary human dermal fibroblasts

“…Enzymatic assays or flow cytometry have been used to assess active molecules for proliferative or apoptotic activities, qPCR can identify genes that regulate fibroblast migration/ECM production and electrical cell-substrate impedance sensing (ECIS) assays [6] give a direct measure of cell migration. CRTAC1 is an ECM protein that was first isolated from human chondrogenic tissue [7] and subsequently described in other vertebrates, non-vertebrate eukaryotes and in some prokaryotes [8,9]. Two splice variants of CRTAC1, with a widespread tissue distribution have been described in humans (a long form hCRTAC1-A and a short form, hCRTAC1-B) [7], which are of interest because of their association with a diversity of diseases of hard and soft tissue [10][11][12].…”

“…Studies in mice that only possess Crtac1B, revealed that in the brain it is a key factor in lateral olfactory tract (LOT) formation, and it was named LOTUS (for LOT usher substance) [14] Crtac1B is also expressed by mice chondrocytes but gene deletion fails to cause an overt phenotype, although in an osteoarthritic model it significantly inhibited cartilage degradation, osteophyte formation and gait abnormalities in females [15]. Structural analysis and modeling of CRTAC1 suggests it may have several yet unexplored functions, it belongs to a family of β-propeller proteins that share several conserved motifs/domains [8,9,16]. The structure of CRTAC1 has been well conserved during its evolution; it has an N-terminal integrin α chain like-domain, an ASPIC/UnbV domain and a C-terminal calcium-binding epidermal growth factor domain (EGF-Ca).…”