Trypanosoma brucei is the causal agent of African Trypanosomiasis in humans and other animals. It maintains a long‐term infection through an antigenic variation based population survival strategy. To proliferate in a mammal, T. brucei acquires iron and haem through the receptor mediated uptake of host transferrin and haptoglobin‐hemoglobin respectively. The receptors are exposed to host antibodies but this does not lead to clearance of the infection. Here we discuss how the trypanosome avoids this fate in the context of recent (...) findings on the structure and cell biology of the receptors. (shrink)

In the 1930s Warburg's spare prose and disciplined respect for the facts set the style for a new generation of biochemists who had not known the conceptual revolutions of earlier years. Led by Warburg, they rejected the excesses of the colloid school and the false starts of the teens and twenties. Talk of active structure virtually disappeared as chemists began to identify enzymes, coenzymes, vitamins, and hormones. In the gradual transformation of the Atmungsferment from an ironcolloid complex to a specific (...) haem-protein, the roots of Warburg's inspiration were readily forgotten-the richer and more varied intellectual currents of the early decades of biochemistry. Experimental cytology and pharmacology were important strands. Most of what Warburg was doing on narcosis from 1908 to 1912 was typical of this school. He was deeply influenced by Loeb and his theory of the fertilization membrane. In the period from 1900 to 1914 the ups and down of belief in Hofmeister's enzyme theory was an important trend which helped determine the style of biochemistry in later decades. Warburg's conception of the Atmungsferment was shaped by the general reaction c. 1910 against Buchner's optimistic view. Warburg's Heidelberg lecture was framed as an answer to Hofmeister's lecture of 1901 and turned out almost as an imitation or second edition of it. It was a style that was soon out of fashion. The affinity between the early concept of enzymes and the old concept idea of “living protein” should not be neglected in discussions of Warburg's distaste for “enzymology.” The colloid school is too easily dismissed as a mere impediment to the chemical triumphs of the 1930s. Warburg's Atmungsferment was obviously colored by the colloidal cast of biochemical thought in 1912. The Atmungsferment represented, in short, a hybrid transition from the romantic biochemistry of the period 1900–1925 to the mature, classical of the 1930s. It is fascinating precisely because it reflects, and refracts through a unique and powerful mind, the varied local traditions of the early history of modern biochemistry. (shrink)

Vertebrate haemoglobin (Hb), the oxygen‐carrying protein of the blood, consists of two α‐ and two β‐subunits, each containing one haem, and shows cooperative oxygen binding known as the haem–haem interaction. The amino‐acid sequences of Hbs found in different species have diverged considerably and the homology in the most distantly related ones is only 40%. How can such varied amino‐acid sequences give rise to similar three‐dimensional structures and functional properties? To what extent do amino‐acid replacements affect the structure (...) of haemoglobin? Which mutations are responsible for the functional differences between haemoglobins from different species? Expression of α‐ and β‐globins in Escherichia coli has enabled us to introduce any mutations in the haemoglobin molecule at will. By X‐ray crystallographic and functional studies of the engineered mutants, we are trying to answer these questions. (shrink)