Crystal structure of human maspin, a serpin with antitumor properties - Reactive center loop of maspin is exposed but constrained

被引:43
作者
Al-Ayyoubi, M
Gettins, PGW
Volz, K [1 ]
机构
[1] Univ Illinois, Dept Microbiol & Immunol, 835 S Wolcott Ave, Chicago, IL 60612 USA
[2] Univ Illinois, Dept Biochem & Mol Biol, Chicago, IL 60612 USA
关键词
D O I
10.1074/jbc.M409957200
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
Maspin, a member of the serpin superfamily, has tumor suppressing activity against breast and prostate cancer. Maspin inhibits tumor growth by blocking cell invasion, and its reactive center loop (RCL) is thought to mediate this activity. To understand this function on the molecular level, we have solved the three-dimensional structure of Maspin to 3.1 Angstrom resolution. The molecular structure shows the characteristic features of the serpin fold, but the RCL of Maspin is unique in length, composition, and placement. Although the RCL of Maspin is accessible and cleavable by some proteinases, it functions in the uncleaved, constrained conformation observed here. These structural results will contribute to our understanding of the mechanism by which Maspin suppresses tumors.
引用
收藏
页码:55540 / 55544
页数:5
相关论文
共 41 条
[1]   Binding of pigment epithelium-derived factor (PEDF) to retinoblastoma cells and cerebellar granule neurons - Evidence for a PEDF receptor [J].
Alberdi, E ;
Aymerich, MS ;
Becerra, SP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (44) :31605-31612
[2]   Maspin inhibits cell migration in the absence of protease inhibitory activity [J].
Bass, R ;
Fernández, AMM ;
Ellis, V .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (49) :46845-46848
[3]   Evidence for a direct interaction between the tumor suppressor serpin, maspin, and types I and III collagen [J].
Blacque, OE ;
Worrall, DM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) :10783-10788
[4]  
Brunger AT, 1998, ACTA CRYSTALLOGR D, V54, P905, DOI 10.1107/s0907444998003254
[5]   Methylation matters: a new spin on maspin [J].
Costello, JF ;
Vertino, PM .
NATURE GENETICS, 2002, 31 (02) :123-124
[6]   Pigment epithelium-derived factor: A potent inhibitor of angiogenesis [J].
Dawson, DW ;
Volpert, OV ;
Gillis, P ;
Crawford, SE ;
Xu, HJ ;
Benedict, W ;
Bouck, NP .
SCIENCE, 1999, 285 (5425) :245-248
[7]  
Domann FE, 2000, INT J CANCER, V85, P805, DOI 10.1002/(SICI)1097-0215(20000315)85:6<805::AID-IJC12>3.0.CO
[8]  
2-5
[9]   Inhibitory conformation of the reactive loop of alpha(1)-antitrypsin [J].
Elliott, PR ;
Lomas, DA ;
Carrell, RW ;
Abrahams, JP .
NATURE STRUCTURAL BIOLOGY, 1996, 3 (08) :676-681
[10]   Wild-type α1-antitrypsin is in the canonical inhibitory conformation [J].
Elliott, PR ;
Abrahams, JP ;
Lomas, DA .
JOURNAL OF MOLECULAR BIOLOGY, 1998, 275 (03) :419-425