Amino acid sequences caused

Sickle-cell anemia is the classic example of an inherited disease that is caused by a change in a protein s amino acid sequence. Linus Pauling proposed in 1949 that it was caused by a defect in the hemoglobin molecule he thus coined the term molecular disease. Seven years later Vernon Ingram showed that the disease was caused by a single mutation, a change in residue 6 of the P chain of hemoglobin from Glu to Val. 

Intrinsic disorder might not be encoded by the sequence, but rather might be the result of the absence of suitable tertiary interactions. If this were the general cause of intrinsic disorder, any subset of ordered sequences and any subset of disordered sequences would likely be the same within the statistical uncertainty of the sampling. On the other hand, if intrinsic disorder were encoded by the amino acid sequence, any subset of disordered sequences would likely differ significantly from samples of ordered protein sequences. Thus, to test the hypothesis that disorder is encoded by the sequence, we collected examples of intrinsically ordered and intrinsically disordered proteins, then determined whether and how their sequences were distinguishable. 

All botulin neurotoxins act in a similar way. They only differ in the amino-acid sequence of some protein parts (Prabakaran et al., 2001). Botulism symptoms are provoked both by oral ingestion and parenteral injection. Botulin toxin is not inactivated by enzymes present in the gastrointestinal tracts. Foodborne BoNT penetrates the intestinal barrier, presumably due to transcytosis. It is then transported to neuromuscular junctions within the bloodstream and blocks the secretion of the neurotransmitter acetylcholine. This results in muscle limpness and palsy caused by selective hydrolysis of soluble A-ethylmalemide-sensitive factor activating (SNARE) proteins which participate in fusion of synaptic vesicles with presynaptic plasma membrane. SNARE proteins include vesicle-associated membrane protein (VAMP), synaptobrevin, syntaxin, and synaptosomal associated protein of 25 kDa (SNAP-25). Their degradation is responsible for neuromuscular palsy due to blocks in acetylcholine transmission from synaptic terminals. In humans, palsy caused by BoNT/A lasts four to six months. 

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