The factor that determines that two proteins bind lies outside the peptide in an area called the context, according to PLoS One paper.
Researchers at the Institute for Research in Biomedicine (IRB) have unveiled part of the molecular mechanisms for affinity between transient binding proteins. The team points out that these are some of the most complicated interactions to study since they are brief and occur through a large section of the protein surface, called the globular domain and a small section of the surface of a lineal motif, or peptide.
The investigators used computational analysis to explore the 45,000 3-D protein structures currently available on the international database PDB (Protein Data Base). They were able to detect all interactions possible between the globular domain and peptide.
“One of the conclusions from the study is that what determines that two proteins recognize each other as binding partners falls outside the lineal contact motif, in what is called the context,” says Patrick Aloy, ICREA research professor at IRB Barcelona. The contextual residues are amino acids that are found in nearby regions of the lineal motif but do not form part of it.
“The binding strength between two proteins is determined by contacts found in the lineal motif but it is the contextual residues that hold information about the most suitable proteins, thereby preventing undesirable binding between similar proteins,” explains Amelie Stein, a predoctoral student with Aloy’s lab and first author of the article.
The analysis performed by the researchers also revealed that in certain conditions non-native interactions may occur, that is to say, interactions with other proteins that are not optimum. “This is what we refer to as complementary partners; other interaction proteins that can compensate for the lack of the ideal protein,” explains Stein. According to the researchers, these nonoptimum interactions allow for the establishment of emergency circuits that increase the strength of cellular networks.
The study appears in the July 2 issue of PloS One.
