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Structural factors affecting the choice between latency transition and polymerization in inhibitory serpins.

ABSTRACT: Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) protein family, is unique among the serpins in its conformational lability. This lability allows spontaneous conversion of the active form to a more stable, latent conformation under physiological conditions. In other serpins, polymerization, rather than latency transition, is induced under pathological conditions or upon heat treatment. To identify specific factors promoting latency conversion in PAI-1, we mutated PAI-1 at various positions and compared the effects with those of equivalent mutations in alpha(1)-antitrypsin, the archetypal serpin. Mutations that improved interactions with the turn between helix F and the third strand of beta-sheet A (thFs3A) or the fifth strand of beta-sheet A (s5A), which are near the site of latency transition-associated insertion of the reactive center loop, retarded latency conversion but did not greatly increase structural stability. Mutations that decreased interactions with s2C facilitated conformational conversion, possibly by releasing the reactive center loop from beta-sheet C. Mutations of Thr93 that filled a hydrophobic surface pocket on s2A dramatically increased structural stability but had a negligible effect on the conformational transition. Our results suggest that the structural features controlling latency transition in PAI-1 are highly localized, whereas the conformational strain of the native forms of other inhibitory serpins is distributed throughout the molecule and induces polymerization.

SUBMITTER: Yi JY

PROVIDER: S-EPMC2206651 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Structural factors affecting the choice between latency transition and polymerization in inhibitory serpins.

Yi Ji-Yeun JY Im Hana H

Protein science : a publication of the Protein Society 20070330 5

Plasminogen activator inhibitor-1 (PAI-1), a member of the serine protease inhibitor (serpin) protein family, is unique among the serpins in its conformational lability. This lability allows spontaneous conversion of the active form to a more stable, latent conformation under physiological conditions. In other serpins, polymerization, rather than latency transition, is induced under pathological conditions or upon heat treatment. To identify specific factors promoting latency conversion in PAI-1 ...[more]

PMID: 17400919

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Project description:Background:Although stress reaction is high among nursing staff and nursing students in the Middle East and its effect on life is known, there are scant studies reporting on these clinical and social features. In addition, there are no studies reporting on factors that influence career choice among this group. Aim:This study aimed to investigate factors that influence career choice among nursing students and their possible association with depressive symptoms. Method:Participants were 150 (84.7% response rate) nursing students randomly selected from each academic year at the Nursing College/Jordan University of Science and Technology. Participants consented and completed the socio-demographic data collection sheet. The Arabic version of the Beck Depression Inventory-II Scale was used to assess participants with respect to depressive symptoms. A modified list of factors influencing career choice and a Likert scale to assess the level of sadness and the degree of religiosity were used as well. Results:Students ranked the most important three factors influencing their career selection as family decision, religious factors, and the desire to care for others. The prevalence of depression among the sample was 26%. Students who had a desire to care for others were less likely to suffer from depression and those who chose nursing as their career due to religious factors were significantly less depressed than those who did not. Meanwhile, students who chose nursing under family pressure or because of a lack of alternative opportunities were more depressed. The odds ratio for depressive symptoms was 0.24 when students chose nursing because of religious factors, whereas it was 4.92 when the family strongly influenced the student's career decision and 3.61 when a nursing career was the only perceived opportunity available. Conclusion:The main factors associated with depression among this sample of nursing students were pressure from their family to choose a nursing career and having no other career or employment opportunities. Religiosity was negatively associated with depression and may act as a protective factor; however, future studies using longitudinal designs will need to confirm this hypothesis.

Dataset Information

Structural factors affecting the choice between latency transition and polymerization in inhibitory serpins.

Publications

Structural factors affecting the choice between latency transition and polymerization in inhibitory serpins.

Similar Datasets

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