Understanding mechanisms governing protein-protein interactions from synthetic binding interfaces Export

@article{citeulike:3092002, abstract = {Recent advances in methodologies and design of combinatorial library selection have enabled comprehensive characterization of sequence space for protein-protein interaction interfaces and generation of fully synthetic binding interfaces. By exhaustively introducing and quantitatively analyzing mutations in natural interfaces, new insights into their molecular architecture and plasticity have emerged. Minimalist combinatorial libraries based on a restricted amino acid code have produced synthetic interfaces that rival natural ones using a different set of rules. A two amino acid code composed of just tyrosine and serine in the context of antibody CDR loops is sufficient to produce high affinity and specific interactions with different classes of protein targets. Structural analyses highlight the dominant role of Tyr in forming productive interactions and demonstrate the dominance of conformational diversity over chemical diversity in producing na\"{i}ve binding interfaces. Synthetic binding proteins are beginning to be used as a powerful crystallization tool to attack important structural biology problems that are recalcitrant to crystallization using traditional methods.}, author = {Kossiakoff, Anthony A. and Koide, Shohei}, citeulike-article-id = {3092002}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.sbi.2008.06.004}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0959440X08000924}, citeulike-linkout-2 = {http://www.sciencedirect.com/science/article/B6VS6-4T4VMH2-1/2/b46037972c0505b962152ba5695323b7}, doi = {10.1016/j.sbi.2008.06.004}, journal = {Current Opinion in Structural Biology}, keywords = {binding\_domains, interactions, protein-protein}, posted-at = {2008-11-27 05:11:55}, priority = {2}, title = {Understanding mechanisms governing protein-protein interactions from synthetic binding interfaces}, url = {http://dx.doi.org/10.1016/j.sbi.2008.06.004}, volume = {In Press, Corrected Proof} }

TY - JOUR ID - citeulike:3092002 L3 - citeulike-article-id:3092002 N2 - Recent advances in methodologies and design of combinatorial library selection have enabled comprehensive characterization of sequence space for protein-protein interaction interfaces and generation of fully synthetic binding interfaces. By exhaustively introducing and quantitatively analyzing mutations in natural interfaces, new insights into their molecular architecture and plasticity have emerged. Minimalist combinatorial libraries based on a restricted amino acid code have produced synthetic interfaces that rival natural ones using a different set of rules. A two amino acid code composed of just tyrosine and serine in the context of antibody CDR loops is sufficient to produce high affinity and specific interactions with different classes of protein targets. Structural analyses highlight the dominant role of Tyr in forming productive interactions and demonstrate the dominance of conformational diversity over chemical diversity in producing naïve binding interfaces. Synthetic binding proteins are beginning to be used as a powerful crystallization tool to attack important structural biology problems that are recalcitrant to crystallization using traditional methods. JF - Current Opinion in Structural Biology TI - Understanding mechanisms governing protein-protein interactions from synthetic binding interfaces VL - In Press, Corrected Proof KW - binding_domains KW - interactions KW - protein-protein AU - Kossiakoff, Anthony AU - Koide, Shohei UR - http://dx.doi.org/10.1016/j.sbi.2008.06.004 ER -