Stability of domain structures in multi-domain proteins

Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR

Is the level of maternal serum prohepcidin associated with preeclampsia?

Objective: The objective of the study was to compare pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), C-reactive protein (CRP), IL-6 and iron status parameters in preeclamptic (PE) and healthy pregnant women, and to examine the relationship between serum pro-hepcidin levels and iron parameters of preeclampsia (PE). Methods: In a prospective controlled study, we collected serum from women with normal pregnancy (n = 37) and from women with PE (n = 30) at the Department of Obstetrics and Gynecology at Turgut Ozal University between February 2010 and January 2013. Pro-hepcidin, hemoglobin (Hb) concentration, hematocrit (Hct), CRP, IL-6 and iron status parameters were measured in all patients and compared between groups. Results: Levels of serum prohepcidin in PE and control groups were similar and amount 69.4 +/- 19.7 and 71.9 +/- 22.1 ng/ml, respectively. The difference was not statistically significant (p: 0.694). On the other hand, the study group had a statistically lower iron binding capacity (IBC), total iron binding capacity, transferin, total protein, albumin levels (p<0.05). No significant differences were found among prohepcidin, Hb concentration, Hct, iron, ferritin, IL-6, urea and creatine in both the groups. Conclusion: In pregnancies complicated by PE with normal values of hemoglobin and hematocrit, serum prohepcidin concentrations are similar to those observed in healthy pregnant women. The analysis revealed no significant correlations between prohepcidin level and serum iron, serum ferritin or transferrin in the PE