A structural change in the kinesin motor protein that drives motility

Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of an approximately 15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule 'plus' end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when gamma-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.     

The melanocyte differentiation program predisposes to metastasis after neoplastic transformation

The aggressive clinical behavior of melanoma suggests that the developmental origins of melanocytes in the neural crest might be relevant to their metastatic propensity. Here we show that primary human melanocytes, transformed using a specific set of introduced genes, form melanomas that frequently metastasize to multiple secondary sites, whereas human fibroblasts and epithelial cells transformed using an identical set of genes generate primary tumors that rarely do so. Notably, these melanomas have a metastasis spectrum similar to that observed in humans with melanoma. These observations indicate that part of the metastatic proclivity of melanoma is attributable to lineage-specific factors expressed in melanocytes and not in other cell types analyzed. Analysis of microarray data from human nevi shows that the expression pattern of Slug, a master regulator of neural crest cell specification and migration, correlates with those of other genes that are important for neural crest cell migrations during development. Moreover, Slug is required for the metastasis of the transformed melanoma cells. These findings indicate that melanocyte-specific factors present before neoplastic transformation can have a pivotal role in governing melanoma progression.     

Conformational variations in an infectious protein determine prion strain differences

A remarkable feature of prion biology is the strain phenomenon wherein prion particles apparently composed of the same protein lead to phenotypically distinct transmissible states. To reconcile the existence of strains with the 'protein-only' hypothesis of prion transmission, it has been proposed that a single protein can misfold into multiple distinct infectious forms, one for each different strain. Several studies have found correlations between strain phenotypes and conformations of prion particles; however, whether such differences cause or are simply a secondary manifestation of prion strains remains unclear, largely due to the difficulty of creating infectious material from pure protein. Here we report a high-efficiency protocol for infecting yeast with the [PSI+] prion using amyloids composed of a recombinant Sup35 fragment (Sup-NM). Using thermal stability and electron paramagnetic resonance spectroscopy, we demonstrate that Sup-NM amyloids formed at different temperatures adopt distinct, stably propagating conformations. Infection of yeast with these different amyloid conformations leads to different [PSI+] strains. These results establish that Sup-NM adopts an infectious conformation before entering the cell--fulfilling a key prediction of the prion hypothesis--and directly demonstrate that differences in the conformation of the infectious protein determine prion strain variation.     

柳杉树轮δ~(13)C与气候要素的分析与应用

<正>对采自气候为非限制性因子地区的柳杉树轮稳定碳同位素比 δ１３ Ｃ进行气候响应分析。用排除法消除大气二氧化碳中δ１３Ｃ的变化对柳杉树轮δ１３Ｃ变化的影响后,建立残差年序列ＲＥ,并结合西天目山气象站的气象记录,分析了树轮δ１３Ｃ年序列对气候要素的响应。结果表明：西天目山地区树轮 δ１３Ｃ的高频振荡与 １１、１２月最高气温的平均值,１、２、３月降水总和以及６、７月降水总和显著相关,在一定程度上反映了东亚季风对该区的影响大小。可见气候非限制性因子地区树轮稳定碳同位素组成年序列同样可以作为气候变化指针。