Local motions in a benchmark of allosteric proteins

被引:93
作者
Daily, Michael D.
Gray, Jeffrey J.
机构
[1] Johns Hopkins Univ, Program Mol & Computat Biophys, Baltimore, MD 21218 USA
[2] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA
关键词
allosteric protein structure; conformational change; protein motion; protein flexibility; protein crystal structure database;
D O I
10.1002/prot.21300
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Allosteric proteins have been studied extensively in the last 40 years, but so far, no systematic analysis of conformational changes between allosteric structures has been carried out. Here, we compile a set of 51 pairs of known inactive and active allosteric protein structures from the Protein Data Bank. We calculate local conformational differences between the two structures of each protein using simple metrics, such as backbone and side-chain Cartesian displacement, and torsion angle change and rearrangement in residue-residue contacts. Thresholds for each metric arise from distributions of motions in two control sets of pairs of protein structures in the same biochemical state. Statistical analysis of motions in allosteric proteins quantifies the magnitude of allosteric effects and reveals simple structural principles about allostery. For example, allosteric proteins exhibit substantial conformational. changes comprising about 20% of the residues. In addition, motions in allosteric proteins show strong bias toward weakly constrained regions such as loops and the protein surface. Correlation functions show that motions communicate through protein structures over distances averaging 10-20 residues in sequence space and 10-20 A in Cartesian space. Comparison of motions in the allosteric set and a set of 21 nonallosteric ligand-binding proteins shows that nonallosteric proteins also exhibit bias of motion toward weakly constrained regions and local correlation of motion. However, allosteric proteins exhibit twice as much percent motion on average as nonallosteric proteins with ligand-induced motion. These observations may guide efforts to design flexibility and allostery into proteins.
引用
收藏
页码:385 / 399
页数:15
相关论文
共 68 条
  • [1] PRINCIPLES THAT GOVERN FOLDING OF PROTEIN CHAINS
    ANFINSEN, CB
    [J]. SCIENCE, 1973, 181 (4096) : 223 - 230
  • [2] Anisotropy of fluctuation dynamics of proteins with an elastic network model
    Atilgan, AR
    Durell, SR
    Jernigan, RL
    Demirel, MC
    Keskin, O
    Bahar, I
    [J]. BIOPHYSICAL JOURNAL, 2001, 80 (01) : 505 - 515
  • [3] Efficient characterization of collective motions and interresidue correlations in proteins by low-resolution simulations
    Bahar, I
    Erman, B
    Haliloglu, T
    Jernigan, RL
    [J]. BIOCHEMISTRY, 1997, 36 (44) : 13512 - 13523
  • [4] Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential
    Bahar, I
    Atilgan, AR
    Erman, B
    [J]. FOLDING & DESIGN, 1997, 2 (03): : 173 - 181
  • [5] STRUCTURAL MECHANISM FOR GLYCOGEN-PHOSPHORYLASE CONTROL BY PHOSPHORYLATION AND AMP
    BARFORD, D
    HU, SH
    JOHNSON, LN
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1991, 218 (01) : 233 - 260
  • [6] Berg J.M., 2002, Biochemistry, P465
  • [7] The Protein Data Bank
    Berman, HM
    Westbrook, J
    Feng, Z
    Gilliland, G
    Bhat, TN
    Weissig, H
    Shindyalov, IN
    Bourne, PE
    [J]. NUCLEIC ACIDS RESEARCH, 2000, 28 (01) : 235 - 242
  • [8] An analysis of conformational changes on protein-protein association: implications for predictive docking
    Betts, MJ
    Sternberg, MJE
    [J]. PROTEIN ENGINEERING, 1999, 12 (04): : 271 - 283
  • [9] AUTOMATIC-ANALYSIS OF PROTEIN CONFORMATIONAL-CHANGES BY MULTIPLE LINKAGE CLUSTERING
    BOUTONNET, NS
    ROOMAN, MJ
    WODAK, SJ
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1995, 253 (04) : 633 - 647
  • [10] Toward high-resolution de novo structure prediction for small proteins
    Bradley, P
    Misura, KMS
    Baker, D
    [J]. SCIENCE, 2005, 309 (5742) : 1868 - 1871