Proteins of intrinsically disordered structure and their interactions using p53 protein as an example

Abstract

Intrinzično neuređeni proteini čine veliki dio proteoma stanice. Ovdje je opisan samo mali dio strukture, funkcije i interakcija jednog od mnoštva proteina s intrinzično neuređenim dijelovima koji imaju ključne uloge u životu stanice. Suvremena istraživanja daju nam realniji uvid u stanične procese na molekularnoj razini, te mijenjaju sliku proteinskih interakcija. Tek smo na početku i još mnogo posla čeka buduće strukturne biologe u karakterizaciji intrinzične neuređenosti. Naš koncept funkcionalnog proteina kao statičnog entiteta se mijenja u jedan vrlo dinamični i kompleksni. Također fleksibilnost neuređenih struktura zahtijeva razvoj novih eksperimentalnih pristupa za karakterizaciji ponašanja takvih konformacijskih sklopovina. Kao primjer u radu je poslužio protein p53, ali on ne predstavlja nikakvu iznimku. Isti koncepti se mogu primijeniti i na sve ostale intrinzično neuređene proteine s vrlo važnim ulogama u stanici i u patogenezi. Definitivno se polje strukturne biologije usmjerava na proučavanje intrinzične neuređenosti proteina, i gotovo je sigurno da će u bliskoj budućnosti nestrukturna biologija zauzeti većinski dio tematike u udžbenicima molekularne biologije i biokemije.Intrinsically unstructured proteins make up a large part of cell's proteome. Here is described only small part of structure, function and interactions of only one of many proteins with intrinsically unstructured segments that have crucial roles in the cells life. Modern discoveries give us insight into a more realistic picture of cell processes on molecular level and change the concept of protein-protein interactions. We are still at the beginning of the new era of structural biology and lot of work is ahead to fully characterize intrinsic disorder in proteins. Our concept of functional protein changes from a static entity to a very complex and dynamic ensemble. Also, flexibility of disordered structures demands development of new experimental approaches for further characterization of those ensembles. Here, p53 was an example, but it is not an exception. The same concepts are applicable on all the others proteins with unconstructed parts of structure that can be important participants in cell life and pathogenesis. Today, field of structural biology is directed to studying protein disorder, and it is almost certain that in the near future, nonstructural biology will occupy most of the subjects in molecular biology and biochemistry textbooks