Globular protein backbone conformational disorder in crystal structures
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Proteins are not static molecules but dynamic entities able to modify their structure for several reasons, from the necessity to recognize partners to the regulation of their thermodynamic stability. Conformational disorder is frequent in protein structures and atoms can have, in protein crystal structures, two or more alternative, equilibrium positions close to each other. Here, a set of protein crystal structures refined at very high resolution (1 Å or better) is examined to characterize the conformational disorder of the backbone atoms, which is not infrequent: about 15% of the protein backbone atoms are conformationally disordered and three quarters of them have been deposited with two or more equilibrium positions (most of the others were not detected in the electron density maps). Several structural features have been examined and it was observed that Cα atoms tend to be disordered more frequently than the other backbone atoms, likely because their disorder is induced by disordered side chains: side-chain disorder is two times more frequent than backbone disorder. Surprisingly, backbone disorder is only slightly more frequent in loops than in helices and strands and this is in agreement with the observation that backbone disorder is a localized phenomenon: in about 80% of the cases, it is observed in one amino acid and not in its neighbors. However, although backbone disorder does not cluster along the polypeptide sequence, it tends to cluster in 3D, since backbone-disordered amino acids distant in sequence are close in the 3D space.
KeywordsConformational disorder Protein backbone Protein crystal structure
Kristina Djinovic is gratefully acknowledged for her kind hospitality at the University of Vienna and for helpful discussions.
This work was supported by the MIUR-FFABR and by the University of Pavia.
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Conflict of interest
The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
- Atkins P, de Paula J (2014) Physical chemistry: thermodynamics, structure and change. W. H. Freeman, OxfordGoogle Scholar
- Hubbard SJ, Thornton JM (1993) NACCESS. Department of Biochemistry and Molecular Biology, University College, LondonGoogle Scholar
- Lesk AM (2016) Introduction to protein science, 3rd edn. Oxford University Press, OxfordGoogle Scholar
- Piovesan D, Tabaro F, Mičetić I, Necci M, Quaglia F, Oldfield CJ, Aspromonte MC, Davey NE, Davidović R, Dosztányi Z, Elofsson A, Gasparini A, Hatos A, Kajava AV, Kalmar L, Leonardi E, Lazar T, Macedo-Ribeiro S, Macossay-Castillo M, Meszaros A, Minervini G, Murvai N, Pujols J, Roche DB, Salladini E, Schad E, Schramm A, Szabo B, Tantos A, Tonello F, Tsirigos KD, Veljković N, Ventura S, Vranken W, Warholm P, Uversky VN, Dunker AK, Longhi S, Tompa P, Tosatto SC (2017) DisProt 7.0: a major update of the database of disordered proteins. Nucleic Acids Res 45:D1123–D1124CrossRefPubMedGoogle Scholar
- Tompa P (2010) Structure and function of intrinsically disordered proteins. Chapman & Hall, Boca RatonGoogle Scholar
- Viterbo D (2002) Solution and refinement of crystal structures. In: Giacovazzo C (ed) Fundamentals of crystallography. Oxford University Press, New York, pp 413–501Google Scholar