Open AccessCrystal twinning of human MD‐2 recognizing endotoxin cores of lipopolysaccharide
Author(s) -
Ohto Umeharu,
Satow Yoshinori
Publication year - 2008
Publication title -
journal of synchrotron radiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 99
ISSN - 1600-5775
DOI - 10.1107/s0909049507056531
Subject(s) - crystal twinning , crystallography , tetragonal crystal system , crystal structure , crystal (programming language) , diffraction , molecular replacement , lattice (music) , materials science , reciprocal lattice , chemistry , physics , optics , microstructure , computer science , programming language , acoustics
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 P 4 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.