Structural genomics analysis of uncharacterized protein families overrepresented in human gut bacteria identifies a novel glycoside hydrolase.

BackgroundBacteroides spp. form a significant part of our gut microbiome and are well known for optimized metabolism of diverse polysaccharides. Initial analysis of the archetypal Bacteroides thetaiotaomicron genome identified 172 glycosyl hydrolases and a large number of uncharacterized proteins associated with polysaccharide metabolism.ResultsBT_1012 from Bacteroides thetaiotaomicron VPI-5482 is a protein of unknown function and a member of a large protein family consisting entirely of uncharacterized proteins. Initial sequence analysis predicted that this protein has two domains, one on the N- and one on the C-terminal. A PSI-BLAST search found over 150 full length and over 90 half size homologs consisting only of the N-terminal domain. The experimentally determined three-dimensional structure of the BT_1012 protein confirms its two-domain architecture and structural analysis of both domains suggests their specific functions. The N-terminal domain is a putative catalytic domain with significant similarity to known glycoside hydrolases, the C-terminal domain has a beta-sandwich fold typically found in C-terminal domains of other glycosyl hydrolases, however these domains are typically involved in substrate binding. We describe the structure of the BT_1012 protein and discuss its sequence-structure relationship and their possible functional implications.ConclusionsStructural and sequence analyses of the BT_1012 protein identifies it as a glycosyl hydrolase, expanding an already impressive catalog of enzymes involved in polysaccharide metabolism in Bacteroides spp. Based on this we have renamed the Pfam families representing the two domains found in the BT_1012 protein, PF13204 and PF12904, as putative glycoside hydrolase and glycoside hydrolase-associated C-terminal domain respectively

Degradation of Grassland Ecosystems in the Developing World: The Tragedy of Breaking Coupled Human-Natural Systems

Since Hardin (1968) published his famous theory Tragedy of the Commons supported by examples showing that communal grasslands can be easily overgrazed when herdsman increase their herd numbers, a lot of research has supported the viewpoint that rangeland degradation and desertification in much of the pastoral areas in the developing world are caused by overgrazing (Arnalds and Archer 2000). With increasing focus on change at the global scale, many scientists, guided by the disequilibrium theory, hypothesized that climatic variability and change rather than overgrazing is associated with rangeland degradation. We argue that neither overgrazing nor climate change can alone explain the degradation of rangelands worldwide. In contrast, failure to reconcile emergent issues at the interface between the ecological, economic and social aspects has repeatedly resulted in management and policy actions that do not achieve the objectives of optimizing yield of rangeland products in a sustainable manner. The coupled human and natural systems (CHANS) approach proposed by Liu et al. (2007) can be used to identify applicable approaches for helping pastoral societies worldwide cope with global change by facilitating effective collaboration among social scientists, bio/physical scientists, practitioners, managers, and users to protect and sustain pastoral environments (Dong et al. 2011)

Two Pfam protein families characterized by a crystal structure of protein lpg2210 from Legionella pneumophila.

BackgroundEvery genome contains a large number of uncharacterized proteins that may encode entirely novel biological systems. Many of these uncharacterized proteins fall into related sequence families. By applying sequence and structural analysis we hope to provide insight into novel biology.ResultsWe analyze a previously uncharacterized Pfam protein family called DUF4424 [Pfam:PF14415]. The recently solved three-dimensional structure of the protein lpg2210 from Legionella pneumophila provides the first structural information pertaining to this family. This protein additionally includes the first representative structure of another Pfam family called the YARHG domain [Pfam:PF13308]. The Pfam family DUF4424 adopts a 19-stranded beta-sandwich fold that shows similarity to the N-terminal domain of leukotriene A-4 hydrolase. The YARHG domain forms an all-helical domain at the C-terminus. Structure analysis allows us to recognize distant similarities between the DUF4424 domain and individual domains of M1 aminopeptidases and tricorn proteases, which form massive proteasome-like capsids in both archaea and bacteria.ConclusionsBased on our analyses we hypothesize that the DUF4424 domain may have a role in forming large, multi-component enzyme complexes. We suggest that the YARGH domain may play a role in binding a moiety in proximity with peptidoglycan, such as a hydrophobic outer membrane lipid or lipopolysaccharide

Family Structure Stability and Transitions, Parental Involvement, and Educational Outcomes

The family environments children live in have profound effects on the skills, resources, and attitudes those children bring to school. Researchers studying family structure have found that children who live with two married, opposite-sex, biological parents, on average, have better educational outcomes than children living in alternate family structures, perhaps due to higher resources, lower stressors, or different selectivity patterns. Socioeconomic stratification plays a major role in family structure, with low-income families seeing more instability. We argue that the impact of family structure is attenuated by transitions in and out of family structures that may decrease a specific resource important to child academic outcomes: parental involvement. This may contribute to increased academic differences already noted across class gaps. Using waves 1 to 6 of the Growing Up in Australia: Longitudinal Study of Australian Children (LSAC) data, we examine the relationship of family stability and transitions from birth to age 10/11 years on parental involvement and educational outcomes, adjusted for resource, stressor, and selectivity covariates. We find that changes in parental involvement are only apparent for families that experience both a transition and single parenting, and that these differences in parental involvement impact academic outcome

Gut stem cell aging is driven by mTORC1 via a p38 MAPK-p53 pathway.

Nutrients are absorbed solely by the intestinal villi. Aging of this organ causes malabsorption and associated illnesses, yet its aging mechanisms remain unclear. Here, we show that aging-caused intestinal villus structural and functional decline is regulated by mTORC1, a sensor of nutrients and growth factors, which is highly activated in intestinal stem and progenitor cells in geriatric mice. These aging phenotypes are recapitulated in intestinal stem cell-specific Tsc1 knockout mice. Mechanistically, mTORC1 activation increases protein synthesis of MKK6 and augments activation of the p38 MAPK-p53 pathway, leading to decreases in the number and activity of intestinal stem cells as well as villus size and density. Targeting p38 MAPK or p53 prevents or rescues ISC and villus aging and nutrient absorption defects. These findings reveal that mTORC1 drives aging by augmenting a prominent stress response pathway in gut stem cells and identify p38 MAPK as an anti-aging target downstream of mTORC1