Protein Science, Vol 3, Issue 12 2194-2206, Copyright © 1994 by Cold Spring Harbor Laboratory Press

ARTICLE

Cavities and packing at protein interfaces

S. J. HUBBARD and P. ARGOS
European Molecular Biology Laboratory, Postfach 10.2209, Meyerhofstrasse 1, 69012 Heidelberg, Germany

An analysis of internal packing defects or ``cavities'' (both empty and water-containing) within protein structures has been undertaken and includes 3 cavity classes: within domains, between domains, and between protein subunits. We confirm several basic features common to all cavity types but also find a number of new characteristics, including those that distinguish the classes. The total cavity volume remains only a small fraction of the total protein volume and yet increases with protein size. Water-filled ``cavities'' possess a more polar surface and are typically larger. Their constituent waters are necessary to satisfy the local hydrogen bonding potential. Cavitysurrounding atoms are observed to be, on average, less flexible than their environments. Intersubunit and inter-domain cavities are on average larger than the intradomain cavities, occupy a larger fraction of their resident surfaces, and are more frequently water-filled. We observe increased cavity volume at domain-domain interfaces involved with shear type domain motions. The significance of interfacial cavities upon subunit and domain shape complementarity and the protein docking problem, as well as in their structural and functional role in oligomeric proteins, will be discussed. The results concerning cavity size, polarity, solvation, general abundance, and residue type constituency should provide useful guidelines for protein modeling and design.
CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				R. G. Eckenhoff Why Can All of Biology Be Anesthetized? Anesth. Analg., September 1, 2008; 107(3): 859 - 861. [Full Text] [PDF]

				M. Bueno, L. A. Campos, J. Estrada, and J. Sancho Energetics of aliphatic deletions in protein cores. Protein Sci., August 1, 2006; 15(8): 1858 - 1872. [Abstract] [Full Text] [PDF]

				C. Winter, A. Henschel, W. K. Kim, and M. Schroeder SCOPPI: a structural classification of protein-protein interfaces Nucleic Acids Res., January 1, 2006; 34(suppl_1): D310 - D314. [Abstract] [Full Text] [PDF]

				R. Murali, X. Cheng, A. Berezov, X. Du, A. Schon, E. Freire, X. Xu, Y. H. Chen, and M. I. Greene Disabling TNF receptor signaling by induced conformational perturbation of tryptophan-107 PNAS, August 2, 2005; 102(31): 10970 - 10975. [Abstract] [Full Text] [PDF]

				C. R. Buttner, G. R. Cornelis, D. W. Heinz, and H. H. Niemann Crystal structure of Yersinia enterocolitica type III secretion chaperone SycT Protein Sci., August 1, 2005; 14(8): 1993 - 2002. [Abstract] [Full Text] [PDF]

				J. Xi, R. Liu, G. R. Asbury, M. F. Eckenhoff, and R. G. Eckenhoff Inhalational Anesthetic-binding Proteins in Rat Neuronal Membranes J. Biol. Chem., May 7, 2004; 279(19): 19628 - 19633. [Abstract] [Full Text] [PDF]

				T. Kajander, L. Lehtio, M. Schlomann, and A. Goldman The structure of Pseudomonas P51 Cl-muconate lactonizing enzyme: Co-evolution of structure and dynamics with the dehalogenation function Protein Sci., September 1, 2003; 12(9): 1855 - 1864. [Abstract] [Full Text] [PDF]

				S. Jiang, A. Tovchigrechko, and I. A. Vakser The role of geometric complementarity in secondary structure packing: A systematic docking study Protein Sci., August 1, 2003; 12(8): 1646 - 1651. [Abstract] [Full Text] [PDF]

				P. W. White, S. Titolo, K. Brault, L. Thauvette, A. Pelletier, E. Welchner, L. Bourgon, L. Doyon, W. W. Ogilvie, C. Yoakim, et al. Inhibition of Human Papillomavirus DNA Replication by Small Molecule Antagonists of the E1-E2 Protein Interaction J. Biol. Chem., July 11, 2003; 278(29): 26765 - 26772. [Abstract] [Full Text] [PDF]

				K. Takano, Y. Yamagata, and K. Yutani Buried water molecules contribute to the conformational stability of a protein Protein Eng. Des. Sel., January 1, 2003; 16(1): 5 - 9. [Abstract] [Full Text] [PDF]

				R. G. Eckenhoff PROMISCUOUS LIGANDS AND ATTRACTIVE CAVITIES: How do the inhaled anesthetics work? Mol. Interv., December 1, 2001; 1(5): 258 - 268. [Abstract] [Full Text] [PDF]

				P. Durand, S. Fabrega, B. Henrissat, J.-P. Mornon, and P. Lehn Structural features of normal and mutant human lysosomal glycoside hydrolases deduced from bioinformatics analysis Hum. Mol. Genet., April 1, 2000; 9(6): 967 - 977. [Abstract] [Full Text] [PDF]

				I. S. Efimova, A. Salminen, P. Pohjanjoki, J. Lapinniemi, N. N. Magretova, B. S. Cooperman, A. Goldman, R. Lahti, and A. A. Baykov Directed Mutagenesis Studies of the Metal Binding Site at the Subunit Interface of Escherichia coli Inorganic Pyrophosphatase J. Biol. Chem., February 5, 1999; 274(6): 3294 - 3299. [Abstract] [Full Text] [PDF]

				K. F. Ahmad, C. K. Engel, and G. G. Prive Crystal structure of the BTB domain from PLZF PNAS, October 13, 1998; 95(21): 12123 - 12128. [Abstract] [Full Text] [PDF]

				B. Vallone, A. E. Miele, P. Vecchini, E. Chiancone, and M. Brunori Free energy of burying hydrophobic residues in the interface between protein subunits PNAS, May 26, 1998; 95(11): 6103 - 6107. [Abstract] [Full Text] [PDF]

				R. G. Eckenhoff and J. S. Johansson Molecular Interactions Between Inhaled Anesthetics and Proteins Pharmacol. Rev., December 1, 1997; 49(4): 343 - 368. [Abstract] [Full Text] [PDF]