The crystallographic structures show that short stretches from amyloid-prone regions of amyloidogenic proteins run perpendicular to the filament axis, consistent with the "cross-β" feature of amyloid structure. They also reveal a number of characteristics of amyloid structures – neighboring β-sheets are tightly packed together via an interface devoid of water (therefore referred to as dry interface), with the opposing β-strands slightly offset from each other such that their side-chains interdigitate. This compact dehydrated interface created was termed a steric-zipper interface. There are eight theoretical classes of steric-zipper interfaces, dictated by the directionality of the β-sheets (parallel and anti-parallel) and symmetry between adjacent β-sheets. A limitation of X-ray crystallography for solving amyloid structure is represented by the need to form microcrystals, which can be achieved only with peptides shorter than those associated with disease. Although bona fide amyloid structures always are based on intermolecular β-sheets, different types of "higher order" tertiary folds have been observed or proposed. The β-sheets may form a β-sandwich, or a β-solenoid which may be either β-helix or β-roll. Native-like amyloid fibrils in which native β-sheet containing proteins maintain their native-like structure in the fibrils have also been proposed.One complicating factor in studies of amyloidogenic polypeptides is that identical polypeptides can fold into multiple distinct amyloid conformations. This phenomenon is typically described as amyloid polymorphism. It has notable biological consequences given that it is thought to explain the prion strain phenomenon. Formation
Amyloid is formed through the polymerization of hundreds to thousands of monomeric peptides or proteins into long fibers.
The disease developed without any prior warning, with patients complaining of a loss of sensation and numbness in their hands and feet. They became unable to grasp small objects or fasten buttons. They could not run or walk without stumbling, their voices changed in pitch, and many patients complained of difficulties seeing, hearing, and swallowing. In general, these symptoms worsened and were followed by severe convulsions, coma, and eventually death. By October 1956, forty patients had been discovered, fourteen of whom had died: an alarming case fatality rate of 35%. Finding the cause
Researchers from Kumadai also began to focus on the cause of the strange disease. They found that the victims, often members of the same family, were clustered in fishing hamlets along the shore of Minamata Bay. The staple food of victims was invariably fish and shellfish from Minamata Bay. The cats in the local area, which tended to eat scraps from the family table, had died with symptoms similar to those now discovered in humans. This led the researchers to believe that the outbreak was caused by some kind of food poisoning, with contaminated fish and shellfish being the prime suspects. On 4 November, the research group announced its initial findings: "Minamata disease is rather considered to be poisoning by a heavy metal, presumably it enters the human body mainly through fish and shellfish." Identification of mercury
As soon as the investigation identified a heavy metal as the causal substance, the wastewater from the Chisso factory was immediately suspected as the origin.