Mapping the collagen-binding site in the von Willebrand factor-A3 domain

The multimeric glycoprotein von Willebrand factor (VWF) mediates platelet adhesion to collagen at sites of vascular damage. The binding site for collagen types I and III is located in the VWF-A3 domain. Recently, we showed that His(1023), located near the edge between the "front" and "bottom" faces of A3, is critical for collagen binding (Romijn, R. A., Bouma, B., Wuyster, W., Gros, P., Kroon, J., Sixma, J. J., and Huizinga, E. G. (2001) J. Biol. Chem. 276, 9985-9991). To map the binding site in detail, we introduced 22 point mutations in the front and bottom faces of A3. The mutants were expressed as multimeric VWF, and binding to collagen type III was evaluated in a solid-state binding assay and by surface plasmon resonance. Mutation of residues Asp(979), Ser(1020), and His(1023) nearly abolished collagen binding, whereas mutation of residues Ile(975), Thr(977), Val(997), and Glu(1001) reduced binding affinity about 10-fold. Together, these residues define a flat and rather hydrophobic collagen-binding site located at the front face of the A3 domain. The collagen-binding site of VWF-A3 is distinctly different from that of the homologous integrin alpha(2) I domain, which has a hydrophilic binding site located at the top face of the domain. Based on the surface characteristics of the collagen-binding site of A3, we propose that it interacts with collagen sequences containing positively charged and hydrophobic residues. Docking of a collagen triple helix on the binding site suggests a range of possible engagements and predicts that at most eight consecutive residues in a collagen triple helix interact with A3.     

Distributional niche of relatively rare sable antelope in a South African savanna: habitat versus biotic relationships

The geographic distribution of a species is governed by climatic conditions, topography, resources and habitat structure determining the fundamental niche, while the local distribution expressed via home range occupation may be compressed by biotic interactions with competitors and predators, restricting the realised niche. Biotic influences could be especially important for relatively rare species. We investigated how rainfall, geology, land type and abundance of other ungulate species serving as competitors or prey for predators contributed to the patchy distribution of sable antelope herds within Kruger National Park. Data were provided by annual aerial surveys of ungulate populations conducted between 1978 and 1988. Sable herds were more commonly present on granitic and sandstone substrates than on more fertile basalt. They occurred both in the moist south‐west and dry north of the park. They were most abundant in sour bushveld and mopane savanna woodland, and mostly absent from knob thorn‐marula parkland. The presence of sable was negatively associated with high concentrations of impala and wildebeest, less consistently related to the abundance of zebra, and positively associated with the occurrence of buffalo herds. Best supported models included the separate effects of the most abundant grazers along with land type. Interspecific relationships seemed more consistent with vulnerability to predation as the underlying mechanism restricting the distribution of sable herds than with competitive displacement. Sable favoured land types distinct from those where wildebeest, the most preferred prey of lions, and impala, numerically the most important resident prey species, were most abundant. Hence the risk of predation, associated with habitat conditions where abundant prey species are most concentrated, can exert an overriding influence on the distribution of rarer species in terms of their home range occupation.     

Physiological responses to protein aggregates: Fibrinolysis, coagulation and inflammation (new roles for old factors)

Misfolding is an inherent and potentially problematic propensity of proteins. Misfolded proteins tend to aggregate and the deposition of aggregated proteins is associated with a variety of highly debilitating diseases known as amyloidoses. Protein misfolding and aggregation is also increasingly recognized as the underlying cause of other health problems, including atherosclerosis and immunogenicity of biopharmaceuticals. This raises the question how nature deals with the removal of obsolete proteins in order to avoid their accumulation and disease. In recent years two proteases, tPA and factor XII, have been identified that specifically recognize aggregates of misfolded proteins. We here review these discoveries that have uncovered new roles for the fibrinolytic system and the contact activation system beyond haemostasis.     

The Haeckelian hijack of Darwinian deism

ABSTRACT

Ernst Haeckel (1834–1919) is most recalled in the history of biology for his Recapitulation Theory and the allegedly fudged illustrations of embryos that he presented in support of that case. Less well known is his contribution to abiogenesis theory, which he incorporated into evolutionary theory. In so doing, Haeckel, a vitriolic atheist, was instrumental in inserting atheism into the evolutionary mindset. While anti-evolution propaganda commonly makes Darwin out to be the villain of the piece, the association of evolution in the broad sense of the word with atheism arises more from the Haeckelian legacy than from Darwin’s initially conciliatory deism or Huxley’s non-committal agnosticism.