Showing papers on "Structural biology published in 2002"
TL;DR: There are now numerous examples of proteins that are unstructured or only partially structured under physiological conditions and yet are nevertheless functional.
1,280 citations
TL;DR: This review discusses the principal features of this peculiar class of proteins, their structure-function relationships, and the underlying molecular mechanisms that allow the functional state of proteins to be maintained under conditions in which they would normally unfold and aggregate.
Abstract: Proteins are linear polymers synthesized by ribosomes from activated amino acids. The product of this biosynthetic process is a polypeptide chain, which has to adopt the unique three-dimensional structure required for its function in the cell. In 1972, Christian Anfinsen was awarded the Nobel Prize for Chemistry for showing that this folding process is autonomous in that it does not require any additional factors or input of energy. Based on in vitro experiments with purified proteins, it was suggested that the correct three-dimensional structure can form spontaneously in vivo once the newly synthesized protein leaves the ribosome. Furthermore, proteins were assumed to maintain their native conformation until they were degraded by specific enzymes. In the last decade this view of cellular protein folding has changed considerably. It has become clear that a complicated and sophisticated machinery of proteins exists which assists protein folding and allows the functional state of proteins to be maintained under conditions in which they would normally unfold and aggregate. These proteins are collectively called molecular chaperones, because, like their human counterparts, they prevent unwanted interactions between their immature clients. In this review, we discuss the principal features of this peculiar class of proteins, their structure ± function relationships, and the underlying molecular mechanisms.
399 citations
TL;DR: A semi-empirical analysis of nitroxide sidechain dynamics in spin-labeled proteins reveals contributions from fluctuations in backbone dihedral angles and rigid-body (collective) motions of α helices as discussed by the authors.
396 citations
TL;DR: A method to test putative interactions on complexes of known 3D structure is described and confirmation for several interactions is provided, in addition to suggesting molecular details of how they occur.
Abstract: Protein–protein interactions are central to most biological processes. Although much recent effort has been put into methods to identify interacting partners, there has been a limited focus on how these interactions compare with those known from three-dimensional (3D) structures. Because comparison of protein interactions often involves considering homologous, but not identical, proteins, a key issue is whether proteins that are homologous to an interacting pair will interact in the same way, or interact at all. Accordingly, we describe a method to test putative interactions on complexes of known 3D structure. Given a 3D complex and alignments of homologues of the interacting proteins, we assess the fit of any possible interacting pair on the complex by using empirical potentials. For studies of interacting protein families that show different specificities, the method provides a ranking of interacting pairs useful for prioritizing experiments. We evaluate the method on interacting families of proteins with multiple complex structures. We then consider the fibroblast growth factor/receptor system and explore the intersection between complexes of known structure and interactions proposed between yeast proteins by methods such as two-hybrids. We provide confirmation for several interactions, in addition to suggesting molecular details of how they occur.
345 citations
TL;DR: It is now indisputable that collagen interacts and forms functional entities with several other macromolecules of the extracellual matrix, as their structure and their functional role become known.
290 citations
TL;DR: This review focuses on two areas of recent advances in ab initio structure prediction-improvements in the energy functions and strategies to search the caldera region of the energy landscapes.
284 citations
TL;DR: Recent developments demonstrate how this information can be integrated to identify canonical determinants of protein structure and function, including those residues that are on protein surfaces that are especially likely to form binding sites.
274 citations
TL;DR: The discovery, structure, function and biosynthesis of the currently known circular proteins are described, including a remarkable family of circular proteins that is additionally braced by a knotted arrangement of disulfide bonds that confers additional stability and topological complexity upon the family.
273 citations
TL;DR: The conservation of fold and a functional binding face amongst many structures provides a model for investigating the evolutionary trajectory of sequence, structure and function.
220 citations
TL;DR: X-ray structures of three different membrane proteins in complex with antibody fragments have been published and antibody binding was either essential for the crystallisation of the membrane protein or it substantially improved the diffraction quality of the crystals.
208 citations
TL;DR: The structures of these RNA-protein complexes are providing valuable insights into the binding modes and functional implications of these interactions.
TL;DR: Experiments in which single molecules of RNA and DNA are stretched, and the resulting force as a function of extension is measured have yielded new information about the physical, chemical and biological properties of these important molecules.
TL;DR: The X-ray structure of the photoreceptor rhodopsin has provided the first atomic-resolution structure of a seven-transmembrane (7-TM) G-protein-coupled receptor, and this has provided an improved template for interpreting the huge body of structure--activity, mutagenesis and affinity labelling data available for related 7-TM receptors.
TL;DR: A combination of structural, biophysical and computational studies is beginning to shed light on the fundamental principles governing this type of modular allostery in eukaryotic signal transduction proteins.
TL;DR: The investigation of deep relationships among different classes of proteins involved in key cellular functions, such as nucleic acid polymerases and other nucleotide-dependent enzymes, indicates that a substantial set of diverse protein domains evolved within the primordial, ribozyme-dominated RNA world.
TL;DR: As the catalytic and regulatory centers of protein synthesis in cells, ribosomes are central to many aspects of cell and structural biology.
TL;DR: Chaperonins are versatile molecular machines that assist the folding of a wide range of substrate proteins by harnessing an ATPase cycle to control access of non-native proteins to hydrophobic binding sites.
TL;DR: This review evaluates knowledge of the functions that are associated with the oligomeric organization of secondary transport proteins, which are a major class of solute-translocation systems in all living species.
TL;DR: The purpose of this review is to focus on the architecture of the C1 complex and the mechanisms underlying its activation and proteolytic activity, with particular emphasis on the modular proteases C1r and C1s.
TL;DR: Three-dimensional domain swapping is focused on revealing the structural basis of domain swapping and a possible role for domain swapping in the regulation of protein aggregation and activity.
TL;DR: A surface patch facing the inside of the torus that is highly evolutionarily conserved and specific for the CCTgamma apical domain is revealed, suggesting that the specificity of this apicaldomain towards its substrate, partially folded tubulin, is conferred by polar and electrostatic interactions.
TL;DR: This review focuses on the use of 'knowledge-based' potentials derived from protein sequence and structure databases in designing proteins and suggests how the study of these empirical potentials might impact the fundamental understanding of the energetic principles of protein structure.
TL;DR: The remarkable similarity of metal-ion-transport and sequestering systems across different species, and the need to continue the research to confirm hypotheses for the molecular mechanisms of transfers of metal ions between proteins, are among the most striking aspects.
TL;DR: The role of the blind prediction contests, such as the Critical Assessment of techniques for protein Structure Prediction (CASP), will be briefly discussed and examples of their applications given.
TL;DR: A comparison of these structures suggests a structural basis for the broad substrate chain length specificity that is a unique feature of these enzymes.
TL;DR: Though SDS-PAGE could analyze the size and the quantity of megadalton proteins, the resolution of HMM proteins is relatively poor, so a newly developed pulse SDS -PAGE would be able to raise theresolution of H MM proteins compared with the conventional SDS/PAGE.
TL;DR: Solid-state NMR is proving to be a valuable biophysical tool for probing structure and dynamics in a wide range of biomolecules.
Journal Article•
TL;DR: In this paper, a pulse SDS-PAGE was proposed to increase the resolution of high-molecular-mass (HMM) proteins by using an agarose IEF gel in the first dimension.
TL;DR: This approach allows deep insights into the structure-function relationships of C1, particularly with respect to the assembly of the C1 complex and the mechanisms underlying its activation and proteolytic activity.
Abstract: The classical complement pathway is a major element of innate immunity against infection, and is also involved in immune tolerance, graft rejection and various pathologies. This pathway is triggered by C1, a multimolecular protease formed from the association of a recognition protein, C1q, and a catalytic subunit, the calcium-dependent tetramer C1s-C1r-C1r-C1s, which comprises two copies of each of the modular proteases C1r and C1s. All activators of the pathway are recognized by the C1q moiety of C1, a process that generates a conformational signal that triggers self-activation of C1r, which in turn activates C1s, the enzyme that mediates specific cleavage of C4 and C2, the C1 substrates. Early work based on biochemical and electron microscopy studies has allowed characterization of the domain structure of the C1 subcomponents and led to a low-resolution model of the complex in which the elongated C1s-C1r-C1r-C1s tetramer folds into a compact, figure-of-8-shaped conformation upon interaction with C1q. The strategy used over the past decade was based on a dissection of the C1 proteins into modular segments to characterize their function and solve their three-dimensional structure by X-ray crystallography or NMR spectroscopy. This approach allows deep insights into the structure-function relationships of C1, particularly with respect to the assembly of the C1 complex and the mechanisms underlying its activation and proteolytic activity.
TL;DR: Results from simulations indicate that structural adaptation of U1A protein and RNA define distinct mechanisms for induced fit, and suggest an important role for intrinsic molecular architecture and substates other than the native form in the specificity of protein-RNA interactions.
Abstract: Molecular dynamics (MD) simulations on stem loop 2 of U1 small nuclear RNA and a construct of the U1A protein were carried out to obtain predictions of the structures for the unbound forms in solution and to elucidate dynamical aspects of induced fit upon binding. A crystal structure of the complex between the U1A protein and stem loop 2 RNA and an NMR structure for the uncomplexed form of the U1A protein are available from Oubridge et al. (Nature, 1994, Vol. 372, pp. 432-438) and Avis et al. (Journal of Molecular Biology, 1996, Vol. 257, pp. 398-411), respectively. As a consequence, U1A-RNA binding is a particularly attractive case for investigations of induced fit in protein-nucleic acid complexation. When combined with the available structural data, the results from simulations indicate that structural adaptation of U1A protein and RNA define distinct mechanisms for induced fit. For the protein, the calculations indicate that induced fit upon binding involves a non-native thermodynamic substate in which the structure is preorganized for binding. In contrast, induced fit of the RNA involves a distortion of the native structure in solution to an unstable form. However, the RNA solution structures predicted from simulation show evidence that structures in which groups of bases are favorably oriented for binding the U1A protein are thermally accessible. These results, which quantify with computational modeling recent proposals on induced fit and conformational capture by Leuillot and Varani (Biochemistry, 2001, Vol. 40, pp. 7947-7956) and by Williamson (Nature Structural Biology, 2000, Vol. 7, pp. 834-837) suggest an important role for intrinsic molecular architecture and substates other than the native form in the specificity of protein-RNA interactions.