Mcg in 2030: new techniques for atomic position determination of immune complexes.
The lambda-type light chain dimer from a patient (Mcg) with multiple myeloma and amyloidosis was a pioneer protein for determining the three-dimensional structures of immunoglobulins, understanding the effects of ligand binding, and exploring the use of combinatorial methods to identify novel peptides complementary to protein active sites. Despite 30 years of intense study, there are still unanswered questions about the structure of the Mcg dimer, especially with respect to positions of hydrogen atoms and solvent molecules. In the present report, we describe two techniques that will help define the roles of solvent in ligand interactions and complex formation with this immunoglobulin fragment: (1) introduction of helium as a cryogenic agent during X-ray data collection; and (2) addition of neutron diffraction analyses. These techniques should provide improved resolution, and a more accurate structure of the Mcg dimer. Resolution enhancements of 0.5 A have been achieved in preliminary experiments with cryogenic helium, as compared with the best X-ray diffraction data obtained previously. In the near future, neutron diffraction studies should produce the first hydrogen structure for the Mcg dimer and help elucidate the ligand preferences and amyloidogenic properties of this eminently useful protein.
Hanson
B Leif
BL
University of Tennessee Oak Ridge Graduate School of Genome Science and Technology, PO Box 2009, Oak Ridge 37831-8080, USA. blm@ornl.gov
Bunick
Gerard J
GJ
Harp
Joel M
JM
Edmundson
Allen B
AB
D000686:Amyloidosis / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry*; D001536:Bence Jones Protein / Q000737:chemistry*; D018360:Crystallography, X-Ray / Q000639:trends; D019281:Dimerization; D005615:Freezing; D006371:Helium; D006801:Humans; D007146:Immunoglobulin lambda-Chains / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000276:immunology; D033363:Neutron Diffraction / Q000639:trends; D009584:Nitrogen; D055672:Static Electricity; D017356:Synchrotrons
D000936:Antigen-Antibody Complex; D007146:Immunoglobulin lambda-Chains; D006371:Helium; D001536:Bence Jones Protein; D009584:Nitrogen