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Crystal structures explain functional differences in the two actin depolymerization factors of the malaria parasite.

ABSTRACT: Apicomplexan parasites, such as the malaria-causing Plasmodium, utilize an actin-based motor for motility and host cell invasion. The actin filaments of these parasites are unusually short, and actin polymerization is under strict control of a small set of regulatory proteins, which are poorly conserved with their mammalian orthologs. Actin depolymerization factors (ADFs) are among the most important actin regulators, affecting the rates of filament turnover in a multifaceted manner. Plasmodium has two ADFs that display low sequence homology with each other and with the higher eukaryotic family members. Here, we show that ADF2, like canonical ADF proteins but unlike ADF1, binds to both globular and filamentous actin, severing filaments and inducing nucleotide exchange on the actin monomer. The crystal structure of Plasmodium ADF1 shows major differences from the ADF consensus, explaining the lack of F-actin binding. Plasmodium ADF2 structurally resembles the canonical members of the ADF/cofilin family.

SUBMITTER: Singh BK

PROVIDER: S-EPMC3151070 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Crystal structures explain functional differences in the two actin depolymerization factors of the malaria parasite.

Singh Bishal K BK Sattler Julia M JM Chatterjee Moon M Huttu Jani J Schüler Herwig H Kursula Inari I

The Journal of biological chemistry 20110801 32

Apicomplexan parasites, such as the malaria-causing Plasmodium, utilize an actin-based motor for motility and host cell invasion. The actin filaments of these parasites are unusually short, and actin polymerization is under strict control of a small set of regulatory proteins, which are poorly conserved with their mammalian orthologs. Actin depolymerization factors (ADFs) are among the most important actin regulators, affecting the rates of filament turnover in a multifaceted manner. Plasmodium ...[more]

PMID: 21832095

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Project description:BackgroundThe sex differences in memory impairment were inconclusive, and the effect of female reproductive factors (age at menarche, age at menopause, and reproductive period) on the differences was not clear. We aimed to examine the sex differences in objective and subjective memory impairment in postmenopausal women and age- and education-matched men and explore whether the differences were differed by female reproductive factors.MethodsData were obtained from the China Health and Retirement Longitudinal Study. Using the case-control matching method, 3,218 paired postmenopausal women and men matched for age and education were selected. Memory was assessed using the three-word recall task and a self-rated question. Poisson regression models with a robust error variance were used.ResultsThe relative risk was 1.22 (95% confidence interval 1.08-1.38) for objective memory impairment in women compared with men (23.87% vs. 27.36%), and 1.51 (1.36-1.67) for subjective memory impairment (39.34% vs. 28.25%) after adjusting the confounders. The higher risk of objective memory impairment in women was different among groups of age at menarche in a linear pattern, with younger age at menarche associated with higher risks of objective memory impairment (p < 0.001 for trend). It was also different among groups of menopausal age and reproductive period in an approximate U-shaped pattern, with a similar risk of objective memory with men in women menopause at 52-53 years and having a reproductive period of 31-33 years and higher risks in women with earlier or later menopause (RRs raging form 1.17 to1.41) and a shorter or longer period of reproduction (RR, 1.23-1.29). The higher risks of subjective memory impairment in women were not different among different groups of reproductive factors.ConclusionsPostmenopausal women were at an increased risk of objective and subjective memory impairment than men. The higher risks in objective memory, but not subjective memory, were varied by age at menarche, age at menopause, and reproductive periods, which may help understand the underlying mechanisms of sex differences in cognitive ageing and guide precise intervention to preventing dementia among older women and men.

Dataset Information

Crystal structures explain functional differences in the two actin depolymerization factors of the malaria parasite.

Publications

Crystal structures explain functional differences in the two actin depolymerization factors of the malaria parasite.

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