TY - JOUR
T1 - Similar chemistry, but different bond preferences in inter versus intra-protein interactions
AU - Cohen, Mati
AU - Reichmann, Dana
AU - Neuvirth, Hani
AU - Schreiber, Gideon
PY - 2008/8/1
Y1 - 2008/8/1
N2 - Proteins fold into a well-defined structure as a result of the collapse of the polypeptide chain, while transient protein-complex formation mainly is a result of binding of two folded individual monomers. Therefore, a protein-protein interface does not resemble the core of monomeric proteins, but has a more polar nature. Here, we address the question of whether the physico-chemical characteristics of intraprotein versus interprotein bonds differ, or whether interfaces are different from folded monomers only in the preference for certain types of interactions. To address this question we assembled a high resolution, nonredundant, protein-protein interaction database consisting of 1374 homodimer and 572 heterodimer complexes, and compared the physico-chemical properties of these interactions between protein interfaces and monomers. We performed extensive statistical analysis of geometrical properties of interatomic interactions of different types: hydrogen bonds, electrostatic interactions, and aromatic interactions. Our study clearly shows that there is no significant difference in the chemistry, geometry, or packing density of individual interactions between interfaces and monomeric structures. However, the distribution of different bonds differs. For example, side-chain-side-chain interactions constitute over 62% of all interprotein interactions, while they make up only 36% of the bonds stabilizing a protein structure. As on average, properties of backbone interactions are different from those of side chains, a quantitative difference is observed. Our findings clearly show that the same knowledge-based potential can be used for protein-binding sites as for protein structures. However, one has to keep in mind the different architecture of the interfaces and their unique bond preference.
AB - Proteins fold into a well-defined structure as a result of the collapse of the polypeptide chain, while transient protein-complex formation mainly is a result of binding of two folded individual monomers. Therefore, a protein-protein interface does not resemble the core of monomeric proteins, but has a more polar nature. Here, we address the question of whether the physico-chemical characteristics of intraprotein versus interprotein bonds differ, or whether interfaces are different from folded monomers only in the preference for certain types of interactions. To address this question we assembled a high resolution, nonredundant, protein-protein interaction database consisting of 1374 homodimer and 572 heterodimer complexes, and compared the physico-chemical properties of these interactions between protein interfaces and monomers. We performed extensive statistical analysis of geometrical properties of interatomic interactions of different types: hydrogen bonds, electrostatic interactions, and aromatic interactions. Our study clearly shows that there is no significant difference in the chemistry, geometry, or packing density of individual interactions between interfaces and monomeric structures. However, the distribution of different bonds differs. For example, side-chain-side-chain interactions constitute over 62% of all interprotein interactions, while they make up only 36% of the bonds stabilizing a protein structure. As on average, properties of backbone interactions are different from those of side chains, a quantitative difference is observed. Our findings clearly show that the same knowledge-based potential can be used for protein-binding sites as for protein structures. However, one has to keep in mind the different architecture of the interfaces and their unique bond preference.
KW - Interaction geometry
KW - Interface symmetry
KW - Protein complex database
KW - Protein packing
KW - Protein-protein interface
UR - http://www.scopus.com/inward/record.url?scp=46449113031&partnerID=8YFLogxK
U2 - 10.1002/prot.21960
DO - 10.1002/prot.21960
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C2 - 18260101
AN - SCOPUS:46449113031
SN - 0887-3585
VL - 72
SP - 741
EP - 753
JO - Proteins: Structure, Function and Genetics
JF - Proteins: Structure, Function and Genetics
IS - 2
ER -