Crystal structure of the Mycoplasma arthritidis-derived mitogen in apo form reveals a 3D domain-swapped dimer.
Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing particular Vbeta elements of T cell receptor. Here, we report the crystal structure of a MAM mutant K201A in apo form (unliganded) at 2.8-A resolutions. We also partially refined the crystal structures of the MAM wild type and another MAM mutant L50A in apo forms at low resolutions. Unexpectedly, the structures of these apo MAM molecules display a three-dimensional domain-swapped dimer. The entire C-terminal domains of these MAM molecules are involved in the domain swapping. Functional analyses demonstrated that the K201A and L50A mutants do not show altered ability to bind to their host receptors and that they stimulate the activation of T cells as efficiently as does the wild type. Structural comparisons indicated that the "reconstituted" MAM monomer from the domain-swapped dimer displays large differences at the hinge regions from the MAM(wt) molecule in the receptor-bound form. Further comparison indicated that MAM has a flexible N-terminal loop, implying that conformational changes could occur upon receptor binding.
Liu
Lihui
L
Wadsworth Center, New York State Department of Health, 120 New Scotland Ave, Albany, NY 12208, USA.
Li
Zhong
Z
Guo
Yi
Y
VanVranken
Sandra J
SJ
Mourad
Walid
W
Li
Hongmin
H
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001059:Apoproteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D006825:Hybridomas / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008934:Mitogens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D045645:Mycoplasma arthritidis / Q000378:metabolism*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D011975:Receptors, Mitogen / Q000737:chemistry; D012996:Solutions; D018089:Superantigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D001059:Apoproteins; D007376:Interleukin-2; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011975:Receptors, Mitogen; D012996:Solutions; D018089:Superantigens