Apolactoferrin structure demonstrates ligand-induced conformational change in transferrins

Proteins of the transferrin family, which contains serum transferrin and lactoferrin, control iron levels in higher animals through their very tight (Kapp approximately 10(20)) but reversible binding of iron. These bilobate molecules have two binding sites, one per lobe, each housing one Fe3+ and the synergistic CO3(2-) ion. Crystallographic studies of human lactoferrin and rabbit serum transferrin in their iron-bound forms have characterized their binding sites and protein structure. Physical studies show that a substantial conformational change accompanies iron binding and release. We have addressed this phenomenon through crystal structure analysis of human apolactoferrin at 2.8 A resolution. In this structure the N-lobe binding cleft is wide open, following a domain rotation of 53 degrees, mediated by the pivoting of two helices and flexing of two interdomain polypeptide strands. Remarkably, the C-lobe cleft is closed, but unliganded. These observations have implications for transferrin function and for binding proteins in general.     

Mutations in the skeletal muscle alpha-actin gene in patients with actin myopathy and nemaline myopathy.

Muscle contraction results from the force generated between the thin filament protein actin and the thick filament protein myosin, which causes the thick and thin muscle filaments to slide past each other. There are skeletal muscle, cardiac muscle, smooth muscle and non-muscle isoforms of both actin and myosin. Inherited diseases in humans have been associated with defects in cardiac actin (dilated cardiomyopathy and hypertrophic cardiomyopathy), cardiac myosin (hypertrophic cardiomyopathy) and non-muscle myosin (deafness). Here we report that mutations in the human skeletal muscle alpha-actin gene (ACTA1) are associated with two different muscle diseases, 'congenital myopathy with excess of thin myofilaments' (actin myopathy) and nemaline myopathy. Both diseases are characterized by structural abnormalities of the muscle fibres and variable degrees of muscle weakness. We have identified 15 different missense mutations resulting in 14 different amino acid changes. The missense mutations in ACTA1 are distributed throughout all six coding exons, and some involve known functional domains of actin. Approximately half of the patients died within their first year, but two female patients have survived into their thirties and have children. We identified dominant mutations in all but 1 of 14 families, with the missense mutations being single and heterozygous. The only family showing dominant inheritance comprised a 33-year-old affected mother and her two affected and two unaffected children. In another family, the clinically unaffected father is a somatic mosaic for the mutation seen in both of his affected children. We identified recessive mutations in one family in which the two affected siblings had heterozygous mutations in two different exons, one paternally and the other maternally inherited. We also identified de novo mutations in seven sporadic probands for which it was possible to analyse parental DNA.     

地球动力学中的简单尺度关系: 压力在地幔对流和地幔柱形成中的作用

实验室数据可通过尺度关系(scaling relations)外推来探讨地幔过程. 在行星内部, 体积压缩是一个重要参数, 因此有必要探讨与体积压缩有关的各种物理量的尺度关系. 本文应用简单的体积压缩尺度关系将实验数据和上地幔的物质状态外推来预测下地幔条件下的物质行为, 这种预测在热力学上是可行的. 所用尺度关系类似于半协调逼近法. 俯冲板片和板块的空间尺度约几百公里, 时间常数约一亿年, 但依体积尺度关系推测, 这些参数值在深部地幔要高出几个数量级. 这些体积尺度关系意味着地幔深部的运动非常缓慢, 并保留有远古特征. 这些结果又意味着地球内部化学分层是不可逆的, 也不支持地幔柱假说.     

Developments in Biological Treatment of Industrial Wastewaters

Since the 1 989Water Act,the UK waterindustry has been privatised,with the soleresponsibility fordischarges to sewer being held bythe Regional Water Companies who are able to setstandards and effluentcharges.The 1 995 Environment Act established theEnvironment Agency that took over theresponsibilities of the National Rivers Authority,her Majesty's Inspectorate of Pollution and theWaste Disposal Authorities (which wereresponsible for controlling solid and hazardouswastes) .The European …