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Background
S100 proteins are a large family of calcium binding proteins present only in vertebrates. They function intra- and extracellularly both as regulators of homeostatic processes and as potent effectors during inflammation. Among these, S100A8 and S100A9 are two major constituents of neutrophils that can assemble into homodimers, heterodimers and higher oligomeric species, including fibrillary structures found in the ageing prostate. Each of these forms assumes specific functions and their formation is dependent on divalent cations, notably calcium and zinc. In particular, zinc appears as a major regulator of S100 protein function in a disease context. Despite this central role, no structural information on how zinc bind to S100A8/S100A9 and regulates their quaternary structure is yet available.Results
Here we report two crystallographic structures of calcium and zinc-loaded human S100A8. S100A8 binds two zinc ions per homodimer, through two symmetrical, all-His tetracoordination sites, revealing a classical His-Zn binding mode for the protein. Furthermore, the presence of a (Zn)2-cacodylate complex in our second crystal form induces ligand swapping within the canonical His4 zinc binding motif, thereby creating two new Zn-sites, one of which involves residues from symmetry-related molecules. Finally, we describe the calcium-induced S100A8 tetramer and reveal how zinc stabilizes this tetramer by tightening the dimer-dimer interface.Conclusions
Our structures of Zn2+/Ca2+-bound hS100A8 demonstrate that S100A8 is a genuine His-Zn S100 protein. Furthermore, they show how zinc stabilizes S100A8 tetramerization and potentially mediates the formation of novel interdimer interactions. We propose that these zinc-mediated interactions may serve as a basis for the generation of larger oligomers in vivo.196.
D. Y. Sumner A. D. Jungblut I. Hawes D. T. Andersen T. J. Mackey K. Wall 《Geobiology》2016,14(6):556-574
Microbial pinnacles in ice‐covered Lake Vanda, McMurdo Dry Valleys, Antarctica, extend from the base of the ice to more than 50 m water depth. The distribution of microbial communities, their photosynthetic potential, and pinnacle morphology affects the local accumulation of biomass, which in turn shapes pinnacle morphology. This feedback, plus environmental stability, promotes the growth of elaborate microbial structures. In Lake Vanda, all mats sampled from greater than 10 m water depth contained pinnacles with a gradation in size from <1‐mm‐tall tufts to pinnacles that were centimeters tall. Small pinnacles were cuspate, whereas larger ones had variable morphology. The largest pinnacles were up to ~30 cm tall and had cylindrical bases and cuspate tops. Pinnacle biomass was dominated by cyanobacteria from the morphological and genomic groups Leptolyngbya, Phormidium, and Tychonema. The photosynthetic potential of these cyanobacterial communities was high to depths of several millimeters into the mat based on PAM fluorometry, and sufficient light for photosynthesis penetrated ~5 mm into pinnacles. The distribution of photosynthetic potential and its correlation to pinnacle morphology suggests a working model for pinnacle growth. First, small tufts initiate from random irregularities in prostrate mat. Some tufts grow into pinnacles over the course of ~3 years. As pinnacles increase in size and age, their interiors become colonized by a more diverse community of cyanobacteria with high photosynthetic potential. Biomass accumulation within this subsurface community causes pinnacles to swell, expanding laminae thickness and creating distinctive cylindrical bases and cuspate tops. This change in shape suggests that pinnacle morphology emerges from a specific distribution of biomass accumulation that depends on multiple microbial communities fixing carbon in different parts of pinnacles. Similarly, complex patterns of biomass accumulation may be reflected in the morphology of elaborate ancient stromatolites. 相似文献
197.
H. H. Andersen Y. Imai K. K. Petersen J. Koenig J. Elberling 《Somatosensory & motor research》2016,33(1):49-60
This study investigated whether itch induced by intra-epidermal histamine is subjected to modulation by a standardized conditioned pain modulation (CPM) paradigm in 24 healthy volunteers. CPM was induced by computer-controlled cuff pressure algometry and histamine was introduced to the volar forearm by skin prick test punctures. Moreover, neurogenic inflammation and wheal reactions induced by histamine and autonomic nervous system responses (heart rate variability and skin conductance) were monitored. CPM did not modulate the intensity of histamine-induced itch suggesting that pruriceptive signaling is not inhibited by pain-recruited endogenous modulation, however, CPM was found to aggravate histamine-induced neurogenic inflammation, likely facilitated by efferent sympathetic fibers. 相似文献
198.
Marianne Ellegaard Øjvind Moestrup Thorbjørn Joest Andersen Nina Lundholm 《欧洲藻类学杂志》2016,51(3):328-337
Resting stages of marine phytoplankton have been shown to have potential for long-term survival and to remain viable in marine sediments for up to about a century. This study documents for the first time long-term survival in haptophytes and prasinophytes, by germination of resting stages of Isochrysis galbana and Mantoniella squamata from up to 40-year-old sediment layers. Germination was induced by setting up sediment slurries in L1 medium at 15°C. Cyst formation was induced in culture strains acquired from the germinations by keeping mixtures of strains in the light or dark at salinities of 20 or 30. The identity of the two species was confirmed by light and electron microscopy as well as LSU and SSU rDNA-based phylogenetic analyses. 相似文献
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Sayantani Chatterjee Ling Y. Lee Rebeca Kawahara Jodie L. Abrahams Barbara Adamczyk Merrina Anugraham Christopher Ashwood Zeynep Sumer‐Bayraktar Matthew T. Briggs Jenny H. L. Chik Arun Everest‐Dass Sarah Frster Hannes Hinneburg Katia R. M. Leite Ian Loke Uwe Mginger Edward S. X. Moh Miyako Nakano Saulo Recuero Manveen K. Sethi Miguel Srougi Kathrin Stavenhagen Vignesh Venkatakrishnan Katherine Wongtrakul‐Kish Simone Diestel Peter Hoffmann Niclas G. Karlsson Daniel Kolarich Mark P. Molloy Michael H. Muders Martin K. Oehler Nicolle H. Packer Giuseppe Palmisano Morten Thaysen‐Andersen 《Proteomics》2019,19(21-22)
While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis. 相似文献
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