Showing papers by "Charles DeLisi published in 1998"
TL;DR: The identification of recurrent structural principles among class I pockets makes it possible to greatly expand the repertoire of known peptide-binding motifs of class I MHC molecules, and the evolutionary strategies underlying the emergence of pocket families are discussed.
118 citations
TL;DR: It is shown that the number of known non-transmembrane protein folds is approximately one half of the total that exist, and that certain superfolds should exist, which accommodate dozens of non-homologous sequence families.
108 citations
TL;DR: A well validated computational docking algorithm is used in conjunction with known crystallographic data to predict the orientation of CH2 when bound to FcRn, and the predicted structure is consistent with all reported mutagenesis data, some of which are explicable only on the basis of the model.
31 citations
TL;DR: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non‐specific adhesion, and incremental stability is found that appears to be related to diffusion‐mediated formation of ternary complex dimers.
Abstract: T cells circulate in blood and the lymphatic system, continually engaging cells through transient non-specific adhesion. In a normally functioning immune system, these interactions permit sufficient time for T-cell receptors (TCRs) to sample major histocompatibility complex (MHC)-peptide complexes for the presence of foreign antigen, with detection of the latter to some extent being triggered by a longer dwell time of the receptor on the complex. Precisely how this incremental stability, which may be relatively small, leads to activation is unclear, but it appears to be related to diffusion-mediated formation of ternary complex dimers. The formation of stable dimers can explain the high sensitivity of the response, but leaves a number of questions unaddressed, including the following: i) How can high sensitivity be reconciled with high specificity, and how can a short TCR dwell time be reconciled with a comparably short time for ternary complex pair formation? ii) What is the nature of the early signals on the plasma membrane that determine alternative responses e.g. proliferation at one extreme and apoptosis at the other? iii) What are the cell-surface correlates of biphasic dose response functions i.e. of responses that peak as a function of dose and then descend? This paper has two loosely coupled goals. One is to review and assess the mathematical and computational methods available for analyzing reactions with and between mobile membrane-bound receptors. These methods range from phenomenological to mechanistic, the latter being based on the details of atomic structure. The other is to apply these methods to address biological questions, such as those raised above, part of whose answer may lie in the kinetic competition between alternative reaction paths.
16 citations
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TL;DR: The main difficulty in understanding solvation phenomena arises from the effects of electrostatics in complex biomolecular systems as discussed by the authors, and the fundamental concepts and methodologies in evaluating electrostatic contributions to solvation.
Abstract: Water serves as a critical solvent for a remarkable array of molecules; in particular it profoundly influences the structure and activity of proteins, and their molecular interactions. Our ability to understand biological processes and to develop innovative applications for biotechnology depend in large part on understanding the biophysics of proteins in their solvated environment. The main difficulty in understanding solvation phenomena arises from the effects of electrostatics in complex biomolecular systems. In this paper we survey and critique the fundamental concepts and methodologies in evaluating electrostatic contributions to solvation.
12 citations