The protein-protein interface evolution acts in a similar way to antibody affinity maturation.
Understanding the evolutionary mechanism that acts at the interfaces of protein-protein complexes is a fundamental issue with high interest for delineating the macromolecular complexes and networks responsible for regulation and complexity in biological systems. To investigate whether the evolution of protein-protein interface acts in a similar way as antibody affinity maturation, we incorporated evolutionary information derived from antibody affinity maturation with common simulation techniques to evaluate prediction success rates of the computational method in affinity improvement in four different systems: antibody-receptor, antibody-peptide, receptor-membrane ligand, and receptor-soluble ligand. It was interesting to find that the same evolutionary information could improve the prediction success rates in all the four protein-protein complexes with an exceptional high accuracy (>57%). One of the most striking findings in our present study is that not only in the antibody-combining site but in other protein-protein interfaces almost all of the affinity-enhancing mutations are located at the germline hotspot sequences (RGYW or WA), indicating that DNA hot spot mechanisms may be widely used in the evolution of protein-protein interfaces. Our data suggest that the evolution of distinct protein-protein interfaces may use the same basic strategy under selection pressure to maintain interactions. Additionally, our data indicate that classical simulation techniques incorporating the evolutionary information derived from in vivo antibody affinity maturation can be utilized as a powerful tool to improve the binding affinity of protein-protein complex with a high accuracy.
Li
Bohua
B
From the International Joint Cancer Institute and 301 General Hospital Cancer Center, Second Military Medical University, Shanghai 200433; the National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering & Antibody, Shanghai 201203, and.
Zhao
Lei
L
From the International Joint Cancer Institute and 301 General Hospital Cancer Center, Second Military Medical University, Shanghai 200433.
Wang
Chong
C
the School of Medicine and School of Pharmacy, The Center for Antibody Medicine of Ministry of Education, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai 200025, China.
Guo
Huaizu
H
the School of Medicine and School of Pharmacy, The Center for Antibody Medicine of Ministry of Education, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai 200025, China.
Wu
Lan
L
From the International Joint Cancer Institute and 301 General Hospital Cancer Center, Second Military Medical University, Shanghai 200433.
Zhang
Xunming
X
From the International Joint Cancer Institute and 301 General Hospital Cancer Center, Second Military Medical University, Shanghai 200433.
Qian
Weizhu
W
From the International Joint Cancer Institute and 301 General Hospital Cancer Center, Second Military Medical University, Shanghai 200433; the National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering & Antibody, Shanghai 201203, and.
Wang
Hao
H
From the International Joint Cancer Institute and 301 General Hospital Cancer Center, Second Military Medical University, Shanghai 200433; the National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering & Antibody, Shanghai 201203, and.
Guo
Yajun
Y
From the International Joint Cancer Institute and 301 General Hospital Cancer Center, Second Military Medical University, Shanghai 200433; the National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering & Antibody, Shanghai 201203, and; the School of Medicine and School of Pharmacy, The Center for Antibody Medicine of Ministry of Education, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai 200025, China. Electronic address: yjguo@smmu.edu.cn.
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived; D000915:Antibody Affinity / Q000235:genetics / Q000276:immunology; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D060908:CTLA-4 Antigen; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D053645:Interleukin-2 Receptor alpha Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000069283:Rituximab; D017386:Sequence Homology, Amino Acid
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D060908:CTLA-4 Antigen; D053645:Interleukin-2 Receptor alpha Subunit; D011506:Proteins; D000069283:Rituximab