STRUCTURAL BASIS FOR THE BINDING OF PROLINE-RICH PEPTIDES TO SH3 DOMAINS

被引:955
作者
YU, HT [1 ]
CHEN, JK [1 ]
FENG, SB [1 ]
DALGARNO, DC [1 ]
BRAUER, AW [1 ]
SCHREIBER, SL [1 ]
机构
[1] ARIAD PHARMACEUT INC, CAMBRIDGE, MA 02139 USA
关键词
D O I
10.1016/0092-8674(94)90367-0
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
A common RXL motif was found in proline rich ligands that were selected from a biased combinatorial peptide library on the basis of their ability to bind specifically to the SH3 domains from phosphatidylinositol 3-kinase (PI3K) or c-Src. The solution structure of the PI3K SH3 domain complexed to one of these ligands, RKLPPRPSK (RLP1), was determined. Structure-based mutations were introduced into the PI3K SH3 domain and the RLP1 ligand, and the influence of these mutations on binding was evaluated. We conclude that SH3 domains recognize proline-rich motifs possessing the left-handed type II polyproline (PPII) helix conformation. Two proline residues directly contact the receptor. Other prolines in the ligands appear to function as a molecular scaffold, promoting the formation of the PPII helix. Three nonproline residues consisting of combinations of arginine and leucine interact extensively with the SH3 domain and appear to confer ligand specificity.
引用
收藏
页码:933 / 945
页数:13
相关论文
共 62 条
[1]   LEFT-HANDED POLYPROLINE-II HELICES COMMONLY OCCUR IN GLOBULAR-PROTEINS [J].
ADZHUBEI, AA ;
STERNBERG, MJE .
JOURNAL OF MOLECULAR BIOLOGY, 1993, 229 (02) :472-493
[2]   PRIMARY STRUCTURE OF HUMAN PROACROSIN DEDUCED FROM ITS CDNA SEQUENCE [J].
BABA, T ;
WATANABE, K ;
KASHIWABARA, S ;
ARAI, Y .
FEBS LETTERS, 1989, 244 (02) :296-300
[3]  
BARFOD ET, 1993, J BIOL CHEM, V268, P26059
[4]   MLEV-17-BASED TWO-DIMENSIONAL HOMONUCLEAR MAGNETIZATION TRANSFER SPECTROSCOPY [J].
BAX, A ;
DAVIS, DG .
JOURNAL OF MAGNETIC RESONANCE, 1985, 65 (02) :355-360
[5]   H-1-H-1 CORRELATION VIA ISOTROPIC MIXING OF C-13 MAGNETIZATION, A NEW 3-DIMENSIONAL APPROACH FOR ASSIGNING H-1 AND C-13 SPECTRA OF C-13-ENRICHED PROTEINS [J].
BAX, A ;
CLORE, GM ;
GRONENBORN, AM .
JOURNAL OF MAGNETIC RESONANCE, 1990, 88 (02) :425-431
[6]   SOLUTION STRUCTURE AND LIGAND-BINDING SITE OF THE SH3 DOMAIN OF THE P85-ALPHA SUBUNIT OF PHOSPHATIDYLINOSITOL 3-KINASE [J].
BOOKER, GW ;
GOUT, I ;
DOWNING, AK ;
DRISCOLL, PC ;
BOYD, J ;
WATERFIELD, MD ;
CAMPBELL, ID .
CELL, 1993, 73 (04) :813-822
[7]  
BRUNGER AT, 1988, XPLOR VERSION 20 MAN
[8]  
BRUNGER AT, 1992, XPLOR VERSION 30 MAN
[9]   EPIDERMAL GROWTH-FACTOR REGULATES P21(RAS) THROUGH THE FORMATION OF A COMPLEX OF RECEPTOR, GRB2 ADAPTER PROTEIN, AND SOS NUCLEOTIDE EXCHANGE FACTOR [J].
BUDAY, L ;
DOWNWARD, J .
CELL, 1993, 73 (03) :611-620
[10]   ONCOGENES AND SIGNAL TRANSDUCTION [J].
CANTLEY, LC ;
AUGER, KR ;
CARPENTER, C ;
DUCKWORTH, B ;
GRAZIANI, A ;
KAPELLER, R ;
SOLTOFF, S .
CELL, 1991, 64 (02) :281-302