A solution structure analysis reveals a bent collagen triple helix in the complement activation recognition molecule mannan-binding lectin.

Collagen triple helices are critical in the function of mannan-binding lectin (MBL), an oligomeric recognition molecule in complement activation. The MBL collagen regions form complexes with the serine proteases MASP-1 and MASP-2 in order to activate complement, and mutations lead to common immunodeficiencies. To evaluate their structure-function properties, we studied the solution structures of four MBL-like collagen peptides.

Enzymatic Phosphorylation of Ser in a Type I Collagen Peptide.

Phosphoproteomics studies have reported phosphorylation at multiple sites within collagen, raising the possibility that these post-translational modifications regulate the physical or biological properties of collagen. In this study, molecular dynamics simulations and experimental studies were carried out on model peptides to establish foundational principles of phosphorylation of Ser residues in collagen. A (Gly-Xaa-Yaa) peptide was designed to include a Ser-containing sequence from type I collagen that was reported to be phosphorylated.

Effects of flexibility of the α2 chain of type I collagen on collagenase cleavage.

Cleavage of collagen by collagenases such as matrix metalloproteinase 1 (MMP-1) is a key step in development, tissue remodeling, and tumor proliferation. The abundant heterotrimeric type I collagen composed of two α1(I) chains and one α2(I) chain is efficiently cleaved by MMP-1 at a unique site in the triple helix, a process which may be initiated by local unfolding within the peptide chains. Atypical homotrimers of the α1(I) chain, found in embryonic and cancer tissues, are very resistant to MMP cleavage.

Collagen Gly missense mutations: Effect of residue identity on collagen structure and integrin binding.

Gly missense mutations in type I collagen, which replace a conserved Gly in the repeating (Gly-Xaa-Yaa) sequence with a larger residue, are known to cause Osteogenesis Imperfecta (OI). The clinical consequences of such mutations range from mild to lethal, with more serious clinical severity associated with larger Gly replacement residues. Here, we investigate the influence of the identity of the residue replacing Gly within and adjacent to the integrin binding GFPGER sequence on triple-helix structure, stability and integrin binding using a recombinant bacterial collagen system.

Economic Impact of Increased Utilization of Multivariate Assay Testing to Guide the Treatment of Ovarian Cancer: Implications for Payers.

Background: Ovarian cancer is the eighth most common cancer among women, but ranks fifth in cancer-related causes of death, the majority of which are detected in late stages, after the cancer has metastasized. The CA125 test is the standard of care for assessing suspicious pelvic masses. However, the primary use of CA125 is to monitor treatment progress rather than to screen for disease, and its sensitivity is exceedingly low, unlike the multivariate assay OVA1.

Non-linearity of the collagen triple helix in solution and implications for collagen function.

Collagen adopts a characteristic supercoiled triple helical conformation which requires a repeating (Xaa-Yaa-Gly) sequence. Despite the abundance of collagen, a combined experimental and atomistic modelling approach has not so far quantitated the degree of flexibility seen experimentally in the solution structures of collagen triple helices. To address this question, we report an experimental study on the flexibility of varying lengths of collagen triple helical peptides, composed of six, eight, ten and twelve repeats of the most stable Pro-Hyp-Gly (POG) units.

BRIDG: a domain information model for translational and clinical protocol-driven research.

Background: It is critical to integrate and analyze data from biological, translational, and clinical studies with data from health systems; however, electronic artifacts are stored in thousands of disparate systems that are often unable to readily exchange data.

Objective: To facilitate meaningful data exchange, a model that presents a common understanding of biomedical research concepts and their relationships with health care semantics is required. The Biomedical Research Integrated Domain Group (BRIDG) domain information model fulfills this need.

Bioengineered Collagens.

There is a great deal of interest in obtaining recombinant collagen as an alternative source of material for biomedical applications and as an approach for obtaining basic structural and biological information. However, application of recombinant technology to collagen presents challenges, most notably the need for post-translational hydroxylation of prolines for triple-helix stability. Full length recombinant human collagens have been successfully expressed in cell lines, yeast, and several plant systems, while collagen fragments have been expressed in E.

Consequences of Glycine Mutations in the Fibronectin-binding Sequence of Collagen.

Collagen and fibronectin (Fn) are two key extracellular matrix proteins, which are known to interact and jointly shape matrix structure and function. Most proteins that interact with collagen bind only to the native triple-helical form, whereas Fn is unusual in binding strongly to denatured collagen and more weakly to native collagen. The consequences of replacing a Gly by Ser at each position in the required (Gly-Xaa-Yaa) Fn-binding sequence are probed here, using model peptides and a recombinant bacterial collagen system.

Mapping the Effect of Gly Mutations in Collagen on α2β1 Integrin Binding.

The replacement of one Gly in the essential repeating tripeptide sequence of the type I collagen triple helix results in the dominant hereditary bone disorder osteogenesis imperfecta. The mechanism leading to pathology likely involves misfolding and autophagy, although it has been hypothesized that some mutations interfere with known collagen interactions. Here, the effect of Gly replacements within and nearby the integrin binding GFPGER sequence was investigated using a recombinant bacterial collagen system.

Affective lability and difficulties with regulation are differentially associated with amygdala and prefrontal response in women with Borderline Personality Disorder.

The present neuroimaging study investigated two aspects of difficulties with emotion associated with Borderline Personality Disorder (BPD): affective lability and difficulty regulating emotion. While these two characteristics have been previously linked to BPD symptomology, it remains unknown whether individual differences in affective lability and emotion regulation difficulties are subserved by distinct neural substrates within a BPD sample. To address this issue, sixty women diagnosed with BPD were scanned while completing a task that assessed baseline emotional reactivity as well as top-down emotion regulation.