Combining multiple structure and sequence alignments to improve sequence detection and alignment: Application to the SH2 domains of Janus kinases

被引:44
作者
Al-Lazikani, B [1 ]
Sheinerman, FB [1 ]
Honig, B [1 ]
机构
[1] Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA
关键词
D O I
10.1073/pnas.011577898
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
In this paper, an approach is described that combines multiple structure alignments and multiple sequence alignments to generate sequence profiles for protein families. First, multiple sequence alignments are generated from sequences that are closely related to each sequence of known three-dimensional structure. These alignments then are merged through a multiple structure alignment of family members of known structure. The merged alignment is used to generate a Hidden Markov Model for the family in question. The Hidden Markov Model can be used to search for new family members or to improve alignments for distantly related family members that already have been identified. Application of a profile generated for SH2 domains indicates that the Janus family of nonreceptor protein tyrosine kinases contains SH2 domains. This conclusion is strongly supported by the results of secondary structure-prediction programs, threading calculations, and the analysis of comparative models generated for these domains. One of the Janus kinases, human TYK2, has an SH2 domain that contains a histidine instead of the conserved arginine at the key phosphotyrosine-binding position, beta B5. Calculations of the pK(a) values of the beta B5 arginines in a number of SH2 domains and of the beta B5 histidine in a homology model of TYK2 suggest that this histidine is likely to be neutral around pH 7, thus indicating that it may have lost the ability to bind phosphotyrosine. If this indeed is the case, TYK2 may contain a domain with an SH2 fold that has a modified binding specificity.
引用
收藏
页码:14796 / 14801
页数:6
相关论文
共 50 条
[31]   Six X-linked agammaglobulinemia-causing missense mutations in the src homology 2 domain of Bruton's tyrosine kinase:: Phosphotyrosine-binding and circular dichroism analysis [J].
Mattsson, PT ;
Lappalainen, I ;
Bäckesjö, CM ;
Brockmann, E ;
Laurén, S ;
Vihinen, M ;
Smith, CIE .
JOURNAL OF IMMUNOLOGY, 2000, 164 (08) :4170-4177
[32]   POINT MUTATIONS IN THE ABL SH2 DOMAIN COORDINATELY IMPAIR PHOSPHOTYROSINE BINDING INVITRO AND TRANSFORMING ACTIVITY INVIVO [J].
MAYER, BJ ;
JACKSON, PK ;
VANETTEN, RA ;
BALTIMORE, D .
MOLECULAR AND CELLULAR BIOLOGY, 1992, 12 (02) :609-618
[33]   Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase [J].
Meng, WY ;
Sawasdikosol, S ;
Burakoff, SJ ;
Eck, MJ .
NATURE, 1999, 398 (6722) :84-90
[34]   A GENERAL METHOD APPLICABLE TO SEARCH FOR SIMILARITIES IN AMINO ACID SEQUENCE OF 2 PROTEINS [J].
NEEDLEMAN, SB ;
WUNSCH, CD .
JOURNAL OF MOLECULAR BIOLOGY, 1970, 48 (03) :443-+
[35]   Combination of threading potentials and sequence profiles improves fold recognition [J].
Panchenko, AR ;
Marchler-Bauer, A ;
Bryant, SH .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 296 (05) :1319-1331
[36]   SMART: identification and annotation of domains from signalling and extracellular protein sequences [J].
Ponting, CP ;
Schultz, J ;
Milpetz, F ;
Bork, P .
NUCLEIC ACIDS RESEARCH, 1999, 27 (01) :229-232
[37]   A 3D-1D substitution matrix for protein fold recognition that includes predicted secondary structure of the sequence [J].
Rice, DW ;
Eisenberg, D .
JOURNAL OF MOLECULAR BIOLOGY, 1997, 267 (04) :1026-1038
[38]  
ROST B, 1994, COMPUT APPL BIOSCI, V10, P53
[39]   COMPARATIVE PROTEIN MODELING BY SATISFACTION OF SPATIAL RESTRAINTS [J].
SALI, A ;
BLUNDELL, TL .
JOURNAL OF MOLECULAR BIOLOGY, 1993, 234 (03) :779-815
[40]  
Sauder JM, 2000, PROTEINS, V40, P6, DOI 10.1002/(SICI)1097-0134(20000701)40:1<6::AID-PROT30>3.0.CO