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Title
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Analogy and solution scattering modelling: new structural strategies for the multidomain proteins of complement, cartilage and the immunoglobulin superfamily.
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Authors
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S.J.Perkins,
C.G.Ullman,
N.C.Brissett,
D.Chamberlain,
M.K.Boehm.
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Ref.
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Immunol Rev, 1998,
163,
237-250.
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PubMed id
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Abstract
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Many immunologically relevant proteins possess multidomain structures. Molecular
structures both at the level of the individual domain and that of the intact
protein are required for a full appreciation of function and control. Two
recently developed structural approaches are reviewed here. Analogy modelling
methods are based on the current understanding of many protein structures, and
make possible the identification of folds for superfamilies of unknown
structures. An integrated multidisciplinary predictive approach has been
successfully applied to the von Willebrand factor type A, proteoglycan tandem
repeat and factor I/membrane attack complex domains. The available experimental
and predictive evidence is assembled in order to identify a known
three-dimensional structure related to the unknown one of interest. Neutron and
X-ray scattering curve modelling provides information on the full multidomain
structure in solution. As scattering curves can be calculated from known atomic
structures, the present availability of structures for many domains in
conjunction with tight constraints based on these structures and the covalent
connections between them results in a small family of allowed best-fit
structures for a given scattering curve. The curve-fit procedure can be
automated, and whole multidomain structures can be determined to a positional
precision of the order of 0.2-1 nm. Such models are informative on the steric
accessibility of each domain and their functional activity, and this is
illustrated for antibody, cell-surface and complement proteins.
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