TY - JOUR
T1 - Structural motifs at protein-protein interfaces
T2 - Protein cores versus two-state and three-state model complexes
AU - Tsai, Chung Jung
AU - Xu, Dong
AU - Nussinov, Ruth
PY - 1997/9
Y1 - 1997/9
N2 - The general similarity in the forces governing protein folding and protein-protein associations has led us to examine the similarity in the architectural motifs between the interfaces and the monomers. We have carried out extensive, all-against-all structural comparisons between the single- chain protein structural dataset and the interface dataset, derived both from all protein-protein complexes in the structural database and from interfaces generated via an automated crystal symmetry operation. We show that despite the absence of chain connections, the global features of the architectural motifs, present in monomers, recur in the interfaces, a reflection of the limited set of the folding patterns. However, although similarity has been observed, the details of the architectural motifs vary. In particular, the extent of the similarity correlates with the consideration of how the interface has been formed. Interfaces derived from two-state model complexes, where the chains fold cooperatively, display a considerable similarity to architectures in protein cores, as judged by the quality of their geometric superposition. On the other hand, the three-state model interfaces, representing binding of already folded molecules, manifest a larger variability and resemble the monomer architecture only in general outline. The origin of the difference between the monomers and the three-state model interfaces can be understood in terms of the different nature of the folding and the binding that are involved. Whereas in the former all degrees of freedom are available to the backbone to maximize favorable interactions, in rigid body, three-state model binding, only six degrees of freedom are allowed. Hence, residue or atom pair-wise potentials derived from protein- protein associations are expected to be less accurate, substantially increasing the number of computationally acceptable alternate binding modes (Finkelstein et el., 1995).
AB - The general similarity in the forces governing protein folding and protein-protein associations has led us to examine the similarity in the architectural motifs between the interfaces and the monomers. We have carried out extensive, all-against-all structural comparisons between the single- chain protein structural dataset and the interface dataset, derived both from all protein-protein complexes in the structural database and from interfaces generated via an automated crystal symmetry operation. We show that despite the absence of chain connections, the global features of the architectural motifs, present in monomers, recur in the interfaces, a reflection of the limited set of the folding patterns. However, although similarity has been observed, the details of the architectural motifs vary. In particular, the extent of the similarity correlates with the consideration of how the interface has been formed. Interfaces derived from two-state model complexes, where the chains fold cooperatively, display a considerable similarity to architectures in protein cores, as judged by the quality of their geometric superposition. On the other hand, the three-state model interfaces, representing binding of already folded molecules, manifest a larger variability and resemble the monomer architecture only in general outline. The origin of the difference between the monomers and the three-state model interfaces can be understood in terms of the different nature of the folding and the binding that are involved. Whereas in the former all degrees of freedom are available to the backbone to maximize favorable interactions, in rigid body, three-state model binding, only six degrees of freedom are allowed. Hence, residue or atom pair-wise potentials derived from protein- protein associations are expected to be less accurate, substantially increasing the number of computationally acceptable alternate binding modes (Finkelstein et el., 1995).
KW - Hydrophobic effect
KW - Motifs
KW - Protein folding
KW - Protein-protein interfaces
KW - Protein-protein recognition
KW - Structural comparison
UR - http://www.scopus.com/inward/record.url?scp=0030768266&partnerID=8YFLogxK
U2 - 10.1002/pro.5560060901
DO - 10.1002/pro.5560060901
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AN - SCOPUS:0030768266
SN - 0961-8368
VL - 6
SP - 1793
EP - 1805
JO - Protein Science
JF - Protein Science
IS - 9
ER -