Improved Helix and Kink Characterization in Membrane Proteins Allows Evaluation of Kink Sequence Predictors

被引:52
作者
Langelaan, David N. [1 ]
Wieczorek, Michal [1 ]
Blouin, Christian [1 ,2 ,3 ]
Rainey, Jan K. [1 ,4 ]
机构
[1] Dalhousie Univ, Dept Biochem & Mol Biol, Halifax, NS B3H 1X5, Canada
[2] Dalhousie Univ, Ctr Genom & Evolutionary Bioinformat, Halifax, NS B3H 1X5, Canada
[3] Dalhousie Univ, Fac Comp Sci, Halifax, NS B3H 1W5, Canada
[4] Dalhousie Univ, Dept Chem, Halifax, NS B3H 4J3, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
ALPHA-HELICES; TRANSMEMBRANE PROTEINS; DATA-BANK; ACTIVATION; GEOMETRY;
D O I
10.1021/ci100324n
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Although the alpha-helical secondary structure of proteins is well-defined, the exact causes and structures of helical kinks are not. This is especially important for transmembrane (TM) helices of integral membrane proteins, many of which contain kinks providing functional diversity despite predominantly helical structure. We have developed a Monte Carlo method based algorithm, MC-HELAN, to determine helical axes alongside positions and angles of helical kinks. Analysis of all nonredundant high-resolution alpha-helical membrane protein structures (842 TM helices from 205 polypeptide chains) revealed kinks in 64% of TM helices, demonstrating that a significantly greater proportion of TM helices are kinked than those indicated by previous analyses. The residue proline is over-represented by a factor >5 if it is two or three residues C-terminal to a bend. Pro lines also cause kinks with larger kink angles than other residues. However, only 33% of TM kinks are in proximity to a proline. Machine learning techniques were used to test for sequence-based predictors of kinks. Although kinks are somewhat predicted by sequence, kink formation appears to be driven predominantly by other factors. This study provides an improved view of the prevalence and architecture of kinks in helical membrane proteins and highlights the fundamental inaccuracy of the typical topological depiction of helical membrane proteins as series of ideal helices.
引用
收藏
页码:2213 / 2220
页数:8
相关论文
共 32 条
  • [1] ICM - A NEW METHOD FOR PROTEIN MODELING AND DESIGN - APPLICATIONS TO DOCKING AND STRUCTURE PREDICTION FROM THE DISTORTED NATIVE CONFORMATION
    ABAGYAN, R
    TOTROV, M
    KUZNETSOV, D
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 1994, 15 (05) : 488 - 506
  • [2] HELIX GEOMETRY IN PROTEINS
    BARLOW, DJ
    THORNTON, JM
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 1988, 201 (03) : 601 - 619
  • [3] 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
  • [4] LIBSVM: A Library for Support Vector Machines
    Chang, Chih-Chung
    Lin, Chih-Jen
    [J]. ACM TRANSACTIONS ON INTELLIGENT SYSTEMS AND TECHNOLOGY, 2011, 2 (03)
  • [5] Creighton T.E., 1996, Proteins Structure and Molecular Properties
  • [6] WebLogo: A sequence logo generator
    Crooks, GE
    Hon, G
    Chandonia, JM
    Brenner, SE
    [J]. GENOME RESEARCH, 2004, 14 (06) : 1188 - 1190
  • [7] 3-DIMENSIONAL STRUCTURE OF MEMBRANE AND SURFACE-PROTEINS
    EISENBERG, D
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 1984, 53 : 595 - 623
  • [8] Position of helical kinks in membrane protein crystal structures and the accuracy of computational prediction
    Hall, Spencer E.
    Roberts, Kyle
    Vaidehi, Nagarajan
    [J]. JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 2009, 27 (08) : 944 - 950
  • [9] Allosteric modulation of a neuronal K+ channel by 1-alkanols is linked to a key residue in the activation gate
    Harris, T
    Graber, AR
    Covarrubias, M
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2003, 285 (04): : C788 - C796
  • [10] DICTIONARY OF PROTEIN SECONDARY STRUCTURE - PATTERN-RECOGNITION OF HYDROGEN-BONDED AND GEOMETRICAL FEATURES
    KABSCH, W
    SANDER, C
    [J]. BIOPOLYMERS, 1983, 22 (12) : 2577 - 2637