Complete crystal structure of monocyte chemotactic protein-2, a CC chemokine that interacts with multiple receptors

被引:51
作者
Blaszczyk, J
Van Coillie, E
Proost, P
Van Damme, J
Opdenakker, G
Bujacz, GD
Wang, JM
Ji, XH [1 ]
机构
[1] NCI, Program Struct Biol, Frederick, MD 21702 USA
[2] NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA
[3] Katholieke Univ Leuven, Lab Mol Immunol, Rega Inst Med Res, B-3000 Louvain, Belgium
[4] Lodz Tech Univ, Inst Tech Biochem, PL-90924 Lodz, Poland
关键词
D O I
10.1021/bi0009340
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
Monocyte chemotactic protein 2 (MCP-2) is a CC chemokine that utilizes multiple cellular receptors to attract and activate human leukocytes. MCP-2 is a potent inhibitor of HIV-1 by virtue of its high-affinity binding to the receptor CCR5, one of the major coreceptors for HIV-1. Although a few structures of CC chemokines have been reported, none of these was determined with the N-terminal pyroglutamic acid residue (pGlu1) and a complete C-terminus. pGlu1 is essential for the chemotactic activity of MCP-2. Recombinant MCP-2 has Gln1 at the N terminus, 12-15% of which cyclizes automatically and forms pGlu1. The chemotactic activity of such MCP-2 mixture, which contains 12-15% pGlu1-form and 85-88% Gln1-form protein, is similar to 10 times lower when compared with that of fully cyclized MCP-2 preparation. Therefore, this chemokine is practically inactive without pGlu1. We have determined the complete crystal structure of MCP-2 that contains both pGlu1 and an intact C-terminus. With the existence of pGlu1, the conformation of the N-terminus allows two additional interactions between the two subunits of MCP-2 dimer: a hydrogen bond between pGlu1 and Asn17 and a salt bridge between Asp3 and Arg18. Consequently, both pGlu1 are anchored and buried, and thereby, both N-terminal regions are protected against protease degradation. We have also observed not previously reported extended helical nature of the C terminal region, which covers residues 58-74.
引用
收藏
页码:14075 / 14081
页数:7
相关论文
共 38 条
[1]  
BAGIOLINI M, 1994, ADV IMMUNOL, V55, P97
[2]   CRYSTAL-STRUCTURE OF INTERLEUKIN-8 - SYMBIOSIS OF NMR AND CRYSTALLOGRAPHY [J].
BALDWIN, ET ;
WEBER, IT ;
STCHARLES, R ;
XUAN, JC ;
APPELLA, E ;
YAMADA, M ;
MATSUSHIMA, K ;
EDWARDS, BFP ;
CLORE, GM ;
GRONENBORN, AM ;
WLODAWER, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (02) :502-506
[3]   Role of the N terminus in RNase a homologues: Differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity [J].
Boix, E ;
Wu, YN ;
Vasandani, VM ;
Saxena, SK ;
Ardelt, W ;
Ladner, J ;
Youle, RJ .
JOURNAL OF MOLECULAR BIOLOGY, 1996, 257 (05) :992-1007
[4]   Crystallographic refinement by simulated annealing: Methods and applications [J].
Brunger, AT ;
Rice, LM .
MACROMOLECULAR CRYSTALLOGRAPHY, PT B, 1997, 277 :243-269
[5]   THE 3-DIMENSIONAL SOLUTION STRUCTURE OF RANTES [J].
CHUNG, CW ;
COOKE, RM ;
PROUDFOOT, AEI ;
WELLS, TNC .
BIOCHEMISTRY, 1995, 34 (29) :9307-9314
[6]   3-DIMENSIONAL STRUCTURE OF INTERLEUKIN-8 IN SOLUTION [J].
CLORE, GM ;
APPELLA, E ;
YAMADA, M ;
MATSUSHIMA, K ;
GRONENBORN, AM .
BIOCHEMISTRY, 1990, 29 (07) :1689-1696
[7]   COMPARISON OF THE SOLUTION NUCLEAR-MAGNETIC-RESONANCE AND CRYSTAL-STRUCTURES OF INTERLEUKIN-8 - POSSIBLE IMPLICATIONS FOR THE MECHANISM OF RECEPTOR-BINDING [J].
CLORE, GM ;
GRONENBORN, AM .
JOURNAL OF MOLECULAR BIOLOGY, 1991, 217 (04) :611-620
[8]   Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation [J].
Crump, MP ;
Rajarathnam, K ;
Kim, KS ;
Clark-Lewis, I ;
Sykes, BD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (35) :22471-22479
[9]   Chemokines and HIV-1 second receptors - Confluence of two fields generates optimism in AIDS research [J].
DSouza, MP ;
Harden, VA .
NATURE MEDICINE, 1996, 2 (12) :1293-1300
[10]   An extensively modified version of MolScript that includes greatly enhanced coloring capabilities [J].
Esnouf, RM .
JOURNAL OF MOLECULAR GRAPHICS & MODELLING, 1997, 15 (02) :132-+