Principles of protein-protein interactions
09 Jan 1996-Proceedings of the National Academy of Sciences of the United States of America (National Academy of Sciences)-Vol. 93, Iss: 1, pp 13-20
TL;DR: This review examines protein complexes in the Brookhaven Protein Databank to gain a better understanding of the principles governing the interactions involved in protein-protein recognition.
Abstract: This review examines protein complexes in the Brookhaven Protein Databank to gain a better understanding of the principles governing the interactions involved in protein-protein recognition. The factors that influence the formation of protein-protein complexes are explored in four different types of protein-protein complexes--homodimeric proteins, heterodimeric proteins, enzyme-inhibitor complexes, and antibody-protein complexes. The comparison between the complexes highlights differences that reflect their biological roles.
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TL;DR: A new method, based on chemical thermodynamics, is developed for automatic detection of macromolecular assemblies in the Protein Data Bank (PDB) entries that are the results of X-ray diffraction experiments, as found, biological units may be recovered at 80-90% success rate, which makesX-ray crystallography an important source of experimental data on macromolescular complexes and protein-protein interactions.
8,377 citations
TL;DR: In this paper, the authors performed an analysis of the recognition sites seen in 75 protein-protein complexes of known three-dimensional structure: 24 protease-inhibitor, 19 antibody-antigen and 32 other complexes, including nine enzymeinhibitors and 11 that are involved in signal transduction.
1,945 citations
TL;DR: It is found that the free energy of binding is not evenly distributed across interfaces; instead, there are hot spots of binding energy made up of a small subset of residues in the dimer interface.
1,902 citations
Cites background or result from "Principles of protein-protein inter..."
...This area is remarkably similar to the minimum interface size observed in previous studies (Jones & Thornton, 1996), yet is less than half of the area buried on the receptor in complex with human growth hormone (1300 AÊ 2)....
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...The vast majority of protein heterodimer interfaces are larger than 600 AÊ 2 (Jones & Thornton, 1996)....
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...Most interfaces are composed of two relatively large protein surfaces with good shape and electrostatic complementarity for one another (Janin, 1995, 1997; Jones & Thornton, 1996; Lawrence & Colman, 1993; McCoy et al., 1997)....
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...At the resolution of individual sidechains, we do not ®nd a correlation between buried hydrophobic surface area and energies, contrary to the results for whole surfaces (Chothia & Janin, 1975; Horton & Lewis, 1992; Jones & Thornton, 1996)....
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...Andrew A. Bogan* and Kurt S. Thorn 0022±2836/98/260001±09 $30.00/0 & Lewis, 1992; Jones & Thornton, 1996; Privalov, 1979)....
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TL;DR: These studies discovered small molecules that bind with drug-like potencies to 'hotspots' on the contact surfaces involved in protein–protein interactions, and bind with much higher efficiencies than do the contact atoms of the natural protein partner.
Abstract: Targeting the interfaces between proteins has huge therapeutic potential, but discovering small-molecule drugs that disrupt protein-protein interactions is an enormous challenge. Several recent success stories, however, indicate that protein-protein interfaces might be more tractable than has been thought. These studies discovered small molecules that bind with drug-like potencies to 'hotspots' on the contact surfaces involved in protein-protein interactions. Remarkably, these small molecules bind deeper within the contact surface of the target protein, and bind with much higher efficiencies, than do the contact atoms of the natural protein partner. Some of these small molecules are now making their way through clinical trials, so this high-hanging fruit might not be far out of reach.
1,801 citations
TL;DR: Several applications of ESI-MS are discussed, including protein interactions with metal ions and nucleic acids and subunit protein structures (quaternary structure) and mass spectrometry offers advantages in speed and sensitivity.
Abstract: Electrospray ionization mass spectrometry has been used to study protein interactions driven by noncovalent forces The gentleness of the electrospray ionization process allows intact protein complexes to be directly detected by mass spectrometry Evidence from the growing body of literature suggests that the ESI-MS observations for these weakly bound systems reflect, to some extent, the nature of the interaction found in the condensed phase Stoichiometry of the complex can be easily obtained from the resulting mass spectrum because the molecular weight of the complex is directly measured For the study of protein interactions, ESI-MS is complementary to other biophysical methods, such as NMR and analytical ultracentrifugation However, mass spectrometry offers advantages in speed and sensitivity The experimental variables that play a role in the outcome of ESI-MS studies of noncovalently bound complexes are reviewed Several applications of ESI-MS are discussed, including protein interactions with metal ions and nucleic acids and subunit protein structures (quaternary structure)
1,137 citations