Structure-based prediction reveals capping motifs that inhibit β-helix aggregation

被引:36
作者
Bryan, Allen W., Jr. [2 ,3 ,4 ]
Starner-Kreinbrink, Jennifer L. [1 ]
Hosur, Raghavendra [4 ]
Clark, Patricia L. [1 ]
Berger, Bonnie [4 ,5 ]
机构
[1] Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA
[2] Harvard Massachusetts Inst Technol MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA
[3] Whitehead Inst, Cambridge, MA 02139 USA
[4] Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA
[5] MIT, Dept Math, Cambridge, MA 02139 USA
关键词
beta-helix; hidden Markov model; threading; aggregation prediction; beta-sheet oligomerization; PROTEIN; ALIGNMENT; DATABASE; FIBRILS; WATER;
D O I
10.1073/pnas.1017504108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The parallel beta-helix is a geometrically regular fold commonly found in the proteomes of bacteria, viruses, fungi, archaea, and some vertebrates. beta-helix structure has been observed in monomeric units of some aggregated amyloid fibers. In contrast, soluble beta-helices, both right-and left-handed, are usually "capped" on each end by one or more secondary structures. Here, an in-depth classification of the diverse range of beta-helix cap structures reveals subtle commonalities in structural components and in interactions with the beta-helix core. Based on these uncovered commonalities, a toolkit of automated predictors was developed for the two distinct types of cap structures. In vitro deletion of the toolkit-predicted C-terminal cap from the pertactin beta-helix resulted in increased aggregation and the formation of soluble oligomeric species. These results suggest that beta-helix cap motifs can prevent specific, beta-sheet-mediated oligomeric interactions, similar to those observed in amyloid formation.
引用
收藏
页码:11099 / 11104
页数:6
相关论文
共 27 条
[1]   BASIC LOCAL ALIGNMENT SEARCH TOOL [J].
ALTSCHUL, SF ;
GISH, W ;
MILLER, W ;
MYERS, EW ;
LIPMAN, DJ .
JOURNAL OF MOLECULAR BIOLOGY, 1990, 215 (03) :403-410
[2]   SCOP database in 2004: refinements integrate structure and sequence family data [J].
Andreeva, A ;
Howorth, D ;
Brenner, SE ;
Hubbard, TJP ;
Chothia, C ;
Murzin, AG .
NUCLEIC ACIDS RESEARCH, 2004, 32 :D226-D229
[3]   3-DIMENSIONAL STRUCTURE OF THE ALKALINE PROTEASE OF PSEUDOMONAS-AERUGINOSA - A 2-DOMAIN PROTEIN WITH A CALCIUM-BINDING PARALLEL-BETA ROLL MOTIF [J].
BAUMANN, U ;
WU, S ;
FLAHERTY, KM ;
MCKAY, DB .
EMBO JOURNAL, 1993, 12 (09) :3357-3364
[4]   Structure of the hexapeptide xenobiotic acetyltransferase from Pseudomonas aeruginosa [J].
Beaman, TW ;
Sugantino, M ;
Roderick, SL .
BIOCHEMISTRY, 1998, 37 (19) :6689-6696
[5]  
Benson DA, 2013, NUCLEIC ACIDS RES, V41, pD36, DOI [10.1093/nar/gkn723, 10.1093/nar/gkp1024, 10.1093/nar/gkw1070, 10.1093/nar/gkr1202, 10.1093/nar/gkx1094, 10.1093/nar/gkl986, 10.1093/nar/gkq1079, 10.1093/nar/gks1195, 10.1093/nar/gkg057]
[6]   The Protein Data Bank [J].
Berman, HM ;
Westbrook, J ;
Feng, Z ;
Gilliland, G ;
Bhat, TN ;
Weissig, H ;
Shindyalov, IN ;
Bourne, PE .
NUCLEIC ACIDS RESEARCH, 2000, 28 (01) :235-242
[7]   BETAWRAP:: Successful prediction of parallel β-helices from primary sequence reveals an association with many microbial pathogens [J].
Bradley, P ;
Cowen, L ;
Menke, M ;
King, J ;
Berger, B .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (26) :14819-14824
[8]   BETASCAN: Probable β-amyloids Identified by Pairwise Probabilistic Analysis [J].
Bryan, Allen W., Jr. ;
Menke, Matthew ;
Cowen, Lenore J. ;
Lindquist, Susan L. ;
Berger, Bonnie .
PLOS COMPUTATIONAL BIOLOGY, 2009, 5 (03)
[9]   Profile hidden Markov models [J].
Eddy, SR .
BIOINFORMATICS, 1998, 14 (09) :755-763
[10]   MUSCLE: a multiple sequence alignment method with reduced time and space complexity [J].
Edgar, RC .
BMC BIOINFORMATICS, 2004, 5 (1) :1-19