Crystal twinning of human MD-2 recognizing endotoxin cores of lipopolysaccharide.

Journal of Synchrotron Radiation
Umeharu Ohto, Yoshinori Satow

Abstract

Twinning of crystals causes overlapping of two or more reciprocal lattice points, and hence structure amplitudes for a single crystalline domain are hardly obtained from X-ray diffraction intensities. MD-2 protein forms a stable complex with Toll-like receptor 4 and recognizes bacterial lipopolysaccharide (LPS). Excessive immune responses activated by LPS cause septic shocks. Saccharide-trimmed human MD-2 crystallizes in the tetragonal form with apparent Laue symmetry of 4/mmm, and diffraction intensities from these crystals indicate crystal twinning. The crystal consists of two different domains, A and B. The c(A) axis of domain A coincides with the c(B) axis of domain B with a smaller lattice, and the a(A) axis corresponds to the (a(B) + b(B)) axis. This twinning severely imposes difficulty in structure determination. Through optimization of cryoprotectant, domain A was thoroughly transformed into domain B. The crystal containing only domain B is in space group P4(1)2(1)2 with one MD-2 molecule in the asymmetric unit. The structure of this form of MD-2 as well as its complex with antiendotoxic lipid IVa was successfully determined using the multiple isomorphous replacement method.

References

Apr 28, 1968·Journal of Molecular Biology·B W Matthews
Jun 11, 2002·Nature Immunology·Yoshinori NagaiKensuke Miyake
Oct 24, 2003·Acta Crystallographica. Section D, Biological Crystallography·Simon Parsons
Oct 24, 2003·Acta Crystallographica. Section D, Biological Crystallography·Zbigniew Dauter
May 26, 2004·Acta Crystallographica. Section D, Biological Crystallography·Lakshmanan GovindasamyRobert McKenna
Jul 28, 2004·Trends in Biochemical Sciences·Monique Gangloff, Nicholas J Gay
Aug 22, 2006·Immunobiology·Alberto VisintinDouglas T Golenbock

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Citations

Jan 21, 2011·Physiological Reviews·Dianhua JiangPaul W Noble

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Methods Mentioned

BETA
glycosylation

Software Mentioned

MOLREP
CCP4
HKL2000
DETWIN

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