Computation-Guided Backbone Grafting of a Discontinuous Motif onto a Protein Scaffold

被引:168
作者
Azoitei, Mihai L. [1 ]
Correia, Bruno E. [1 ,2 ]
Ban, Yih-En Andrew [1 ]
Carrico, Chris [1 ,3 ]
Kalyuzhniy, Oleksandr [1 ]
Chen, Lei [4 ]
Schroeter, Alexandria [1 ]
Huang, Po-Ssu [1 ]
McLellan, Jason S. [4 ]
Kwong, Peter D. [4 ]
Baker, David [1 ,5 ]
Strong, Roland K. [3 ]
Schief, William R. [1 ,6 ,7 ]
机构
[1] Univ Washington, Dept Biochem, Seattle, WA 98195 USA
[2] Inst Gulbenkian Ciencias, PhD Program Computat Biol, Oeiras, Portugal
[3] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98104 USA
[4] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA
[5] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA
[6] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA
[7] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA
关键词
EPITOPE-SCAFFOLDS; HIV-1; GP120; DESIGN; ANTIBODIES; NEUTRALIZATION; SITE;
D O I
10.1126/science.1209368
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The manipulation of protein backbone structure to control interaction and function is a challenge for protein engineering. We integrated computational design with experimental selection for grafting the backbone and side chains of a two-segment HIV gp120 epitope, targeted by the cross-neutralizing antibody b12, onto an unrelated scaffold protein. The final scaffolds bound b12 with high specificity and with affinity similar to that of gp120, and crystallographic analysis of a scaffold bound to b12 revealed high structural mimicry of the gp120-b12 complex structure. The method can be generalized to design other functional proteins through backbone grafting.
引用
收藏
页码:373 / 376
页数:4
相关论文
共 23 条
[1]   An exciting but challenging road ahead for computational enzyme design [J].
Baker, David .
PROTEIN SCIENCE, 2010, 19 (10) :1817-1819
[2]   The Protein Data Bank [J].
Berman, HM ;
Westbrook, J ;
Feng, Z ;
Gilliland, G ;
Bhat, TN ;
Weissig, H ;
Shindyalov, IN ;
Bourne, PE .
NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242
[3]   EFFICIENT NEUTRALIZATION OF PRIMARY ISOLATES OF HIV-1 BY A RECOMBINANT HUMAN MONOCLONAL-ANTIBODY [J].
BURTON, DR ;
PYATI, J ;
KODURI, R ;
SHARP, SJ ;
THORNTON, GB ;
PARREN, PWHI ;
SAWYER, LSW ;
HENDRY, RM ;
DUNLOP, N ;
NARA, PL ;
LAMACCHIA, M ;
GARRATTY, E ;
STIEHM, ER ;
BRYSON, YJ ;
CAO, YZ ;
MOORE, JP ;
HO, DD ;
BARBAS, CF .
SCIENCE, 1994, 266 (5187) :1024-1027
[4]   Isolating and engineering human antibodies using yeast surface display [J].
Chao, Ginger ;
Lau, Wai L. ;
Hackel, Benjamin J. ;
Sazinsky, Stephen L. ;
Lippow, Shaun M. ;
Wittrup, K. Dane .
NATURE PROTOCOLS, 2006, 1 (02) :755-768
[5]   Structure of an unliganded simian immunodeficiency virus gp120 core [J].
Chen, B ;
Vogan, EM ;
Gong, HY ;
Skehel, JJ ;
Wiley, DC ;
Harrison, SC .
NATURE, 2005, 433 (7028) :834-841
[6]   Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120 [J].
Chen, Lei ;
Kwon, Young Do ;
Zhou, Tongqing ;
Wu, Xueling ;
O'Dell, Sijy ;
Cavacini, Lisa ;
Hessell, Ann J. ;
Pancera, Marie ;
Tang, Min ;
Xu, Ling ;
Yang, Zhi-Yong ;
Zhang, Mei-Yun ;
Arthos, James ;
Burton, Dennis R. ;
Dimitrov, Dimiter S. ;
Nabel, Gary J. ;
Posner, Marshall R. ;
Sodroski, Joseph ;
Wyatt, Richard ;
Mascola, John R. ;
Kwong, Peter D. .
SCIENCE, 2009, 326 (5956) :1123-1127
[7]   Computational Design of Epitope-Scaffolds Allows Induction of Antibodies Specific for a Poorly Immunogenic HIV Vaccine Epitope [J].
Correia, Bruno E. ;
Ban, Yih-En Andrew ;
Holmes, Margaret A. ;
Xu, Hengyu ;
Ellingson, Katharine ;
Kraft, Zane ;
Carrico, Chris ;
Boni, Erica ;
Sather, D. Noah ;
Zenobia, Camille ;
Burke, Katherine Y. ;
Bradley-Hewitt, Tyler ;
Bruhn-Johannsen, Jessica F. ;
Kalyuzhniy, Oleksandr ;
Baker, David ;
Strong, Roland K. ;
Stamatatos, Leonidas ;
Schief, William R. .
STRUCTURE, 2010, 18 (09) :1116-1126
[8]   Changing the structural context of a functional beta-hairpin - Synthesis and characterization of a chimera containing the curaremimetic loop of a snake toxin in the scorpion alpha/beta scaffold [J].
Drakopoulou, E ;
ZinnJustin, S ;
Guenneugues, M ;
Gilquin, B ;
Menez, A ;
Vita, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (20) :11979-11987
[9]   Computational Design of Proteins Targeting the Conserved Stem Region of Influenza Hemagglutinin [J].
Fleishman, Sarel J. ;
Whitehead, Timothy A. ;
Ekiert, Damian C. ;
Dreyfus, Cyrille ;
Corn, Jacob E. ;
Strauch, Eva-Maria ;
Wilson, Ian A. ;
Baker, David .
SCIENCE, 2011, 332 (6031) :816-821
[10]   HIGH-RESOLUTION FUNCTIONAL-ANALYSIS OF ANTIBODY-ANTIGEN INTERACTIONS [J].
JIN, L ;
FENDLY, BM ;
WELLS, JA .
JOURNAL OF MOLECULAR BIOLOGY, 1992, 226 (03) :851-865