title: The structure of a polyQ-anti-polyQ complex reveals binding according to a linear lattice model.
abstract: Huntington and related neurological diseases result from expansion of a polyglutamine (polyQ) tract. The linear lattice model for the structure and binding properties of polyQ proposes that both expanded and normal polyQ tracts in the preaggregation state are random-coil structures but that an expanded polyQ repeat contains a larger number of epitopes recognized by antibodies or other proteins. The crystal structure of polyQ bound to MW1, an antibody against polyQ, reveals that polyQ adopts an extended, coil-like structure. Consistent with the linear lattice model, multimeric MW1 Fvs bind more tightly to longer than to shorter polyQ tracts and, compared with monomeric Fv, bind expanded polyQ repeats with higher apparent affinities. These results suggest a mechanism for the toxicity of expanded polyQ and a strategy to link anti-polyQ compounds to create high-avidity therapeutics.
authors: Division of Biology 114-96, California Institute of Technology, Pasadena, California 91125, USA. pingwei@neo.tamu.edu
authors: Pingwei
authors: P
authors: Li
authors: Kathryn E
authors: KE
authors: Huey-Tubman
authors: Tiyu
authors: T
authors: Gao
authors: Xiaojun
authors: X
authors: Li
authors: Anthony P
authors: AP
authors: West
authors: Melanie J
authors: MJ
authors: Bennett
authors: Pamela J
authors: PJ
authors: Bjorkman
mesh_terms: D000906:Antibodies / Q000276:immunology; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D018360:Crystallography, X-Ray; D007128:Immunoglobulin Fragments; D008956:Models, Chemical; D019636:Neurodegenerative Diseases / Q000209:etiology; D010455:Peptides / Q000737:chemistry* / Q000276:immunology* / Q000633:toxicity; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D007128:Immunoglobulin Fragments; D010455:Peptides; C055966:immunoglobulin Fv; C097188:polyglutamine