Am y loid Struc ture: Models and The o ret i cal Con sid er ations in Fi brous Ag gre gates +
G. Lynn, Ami S. Lakdawala, James P. Snyder, C. Liotta · 2002
In celebration of the many con tri bu tions to pep tide chem is try from K.-T. Wang’s lab o ra tory, this manu script ex plores the struc ture of the A (10-35) fi bril. This cen tral seg ment of the A pep tide of Alz hei mer’s Dis ease self-assembles into well-ordered paracrystalline ar rays that seem to con tra dict many of the ac cepted par a digms es tab lished for sol u ble, glob u lar pro teins. Here we ex ploit ini tial mo lec u l ar mod el ing ef forts to as sist in un der stand ing these ap par ent con tra dic tions. The emerg ing struc ture is one of a large self-assembly of -strands, whose sta bil ity is de pend ent on large spa tial and tem po ral fluc tu a tion about a cen tral core, giv ing rise to what can be best de scribed as a dy namic and fluid tube-like mi celle. This fi bril struc ture main tains fea tures that are dis tinctly dif fer ent from those of ei ther syn thetic or bi o log i cal fi brils, and these dif fer ences have pro found im pli ca tions for bio med i cal in ter ven tion in am y loid dis eases as well as for the de sign of selfassembling nanoscale fi brils.