TY - JOUR
T1 - A new, structurally nonredundant, diverse data set of protein-protein interfaces and its implications
AU - Keskin, Ozlem
AU - Tsai, Chung Jung
AU - Wolfson, Haim
AU - Nussinov, Ruth
PY - 2004/4
Y1 - 2004/4
N2 - Here, we present a diverse, structurally nonredundant data set of two-chain protein-protein interfaces derived from the PDB. Using a sequence order-independent structural comparison algorithm and hierarchical clustering, 3799 interface clusters are obtained. These yield 103 clusters with at least five nonhomologous members. We divide the clusters into three types. In Type I clusters, the global structures of the chains from which the interfaces are derived are also similar. This cluster type is expected because, in general, related proteins associate in similar ways. In Type II, the interfaces are similar; however, remarkably, the overall structures and functions of the chains are different. The functional spectrum is broad, from enzymes/inhibitors to immunoglobulins and toxins. The fact that structurally different monomers associate in similar ways, suggests "good" binding architectures. This observation extends a paradigm in protein science: It has been well known that proteins with similar structures may have different functions. Here, we show that it extends to interfaces. In Type III clusters, only one side of the interface is similar across the cluster. This structurally nonredundant data set provides rich data for studies of protein-protein interactions and recognition, cellular networks and drug design. In particular, it may be useful in addressing the difficult question of what are the favorable ways for proteins to interact.
AB - Here, we present a diverse, structurally nonredundant data set of two-chain protein-protein interfaces derived from the PDB. Using a sequence order-independent structural comparison algorithm and hierarchical clustering, 3799 interface clusters are obtained. These yield 103 clusters with at least five nonhomologous members. We divide the clusters into three types. In Type I clusters, the global structures of the chains from which the interfaces are derived are also similar. This cluster type is expected because, in general, related proteins associate in similar ways. In Type II, the interfaces are similar; however, remarkably, the overall structures and functions of the chains are different. The functional spectrum is broad, from enzymes/inhibitors to immunoglobulins and toxins. The fact that structurally different monomers associate in similar ways, suggests "good" binding architectures. This observation extends a paradigm in protein science: It has been well known that proteins with similar structures may have different functions. Here, we show that it extends to interfaces. In Type III clusters, only one side of the interface is similar across the cluster. This structurally nonredundant data set provides rich data for studies of protein-protein interactions and recognition, cellular networks and drug design. In particular, it may be useful in addressing the difficult question of what are the favorable ways for proteins to interact.
KW - Data set of interfaces
KW - Motifs, protein-protein interactions
KW - Protein binding
KW - Protein interfaces
KW - Protein-protein association
UR - http://www.scopus.com/inward/record.url?scp=1842507022&partnerID=8YFLogxK
U2 - 10.1110/ps.03484604
DO - 10.1110/ps.03484604
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AN - SCOPUS:1842507022
SN - 0961-8368
VL - 13
SP - 1043
EP - 1055
JO - Protein Science
JF - Protein Science
IS - 4
ER -