Structural Biochemistry/Intrinsically Disordered Proteins: 10-year recap/Importance and Evidence of Disorder
Importance and Evidence of Disorder edit
Structural disorder taking over edit
For many, many years, heavy evidence has accumulated that a well known protein structure is required to know the exact function of the protein. Many believed that the biological phenomena at the cellular level relied on the structure-function model. Although that the structure-function concept was highly apparent in all proteins, there were small hints and signs that intrinsically disordered proteins had a role in cell functions as well and were vastly left to be of no importance to cellular functions. The importance of intrinsically disordered proteins was revealed not too long ago and it was discovered that many proteins or regions of proteins are intrinsically disordered under native, functional conditions. The evidence for intrinsically disordered regions of proteins was very limited compared to the evidence dealing with the structure-function model; however, the importance of intrinsically disordered regions of proteins sparked interest that began the development of insightful knowledge to such structures.
Expanding evidence for disorder edit
This new concept was relied based on a few experimental observations of disorder in several proteins where as the structure-function model was based on thousands of proteins identified in the Protein Data Bank (PDB). Surprisingly, thousands of the proteins identified in the Protein Data Bank contain disordered regions “that become structured only in the presence of a binding partner, and there are also many regions that are actually missing from electron density maps”.[1] Additional evidence was revealed by other techniques such as NMR and circular dichroism, which led to the creation of DisProt which is a database that contains knowledge on structural disorder. DisProt is now available to identify more than 1300 curated intrinsically disordered proteins or intrinsically disordered regions of proteins.
The discovery and identification of many intrinsically disordered proteins “also enabled the development of sophisticated bioinformatic algorithms for predicting disorder from sequence, which further advanced the field”.[1] About a decade ago, predictor of natural disordered regions (PONDR) was the only sequences available to scientists for predicting disorder; today, one can use about any of 50 different predictors to predict disorder, which are based on several different principles. Structural disorder correlates different states of the protein which restricts the prediction accuracy of predictors by any single approach.
Structural disorder is vast in all protein species based on predictions and due to its strong relationship with regulatory and signaling functions, there is a significantly higher level of disorder in eukaryotes than in prokaryotes. The percentage of structural disorder in eukaryotes and prokaryotes is 15-45% and 10-35% respectively. The notion that structural disorder increases with protein complexity and size; however, the highest levels are disorder are “not witnessed in most complex metazoan eukaryotes, but in single-celled eukaryotes that lead a host-changing lifestyle”.[1]