MAD proteins

Chen, X., Rubock, M.J., and Whitman, M. 1996. A transcriptional partner for MAD proteins in TGF-beta signalling. Nature 383 691-696. 

Fig. 17.2 Top The normal situation the Bub and Mad proteins dissociate from the kinetochore region when the microtubuies are properly aligned. The released Bub/Mad proteins activate a protein (Cdc20) which regulates entry into mitosis and activates the anaphase-promoting complex (APC) and gives the go-ahead fbr entry into the anaphase. Below. The situation when the kinetochore is not attached properly to the microtubules. In this case, the Bub and Mad proteins remain attached to the kinetochore, Cdc20 remains inactive, and APC is not activated. This arrests the cell in metaphase. Thus, the Bub and Mad and Mps-1 proteins in yeast and mammals, respectively, respond to improper assembly of the spindle by arresting cells. (Reproduced with permission of Professor R. A. Weinberg and Nature from Rg. 2 in ref. 8.)...

MAD is a family of genes, regulating mitosis and cell proliferation. (Alitotic arrest deficiency genes). The MAD proteins encoded by these genes form complexes with the transcription factor Myc. 

Massague J. TGFbeta signaling receptors, transducers, and Mad proteins. Cell 1996 85(7) 947-950. 

Leahy, D.J., Hendrickson, W.A., Aukhil, A., Erickson, H.P. 5tructure of a fibronectin type II domain from tenascin phased by MAD analysis of the selenome-thionyl protein. Science 258 987-991, 1992. 

The intensity differences obtained in the diffraction pattern by illuminating such a crystal by x-rays of different wavelengths can be used in a way similar to the method of multiple isomorphous replacement to obtain the phases of the diffracted beams. This method of phase determination which is called Multiwavelength Anomalous Diffraction, MAD, and which was pioneered by Wayne Hendrickson at Columbia University, US, is now increasingly used by protein cystallographers. 

MAD multiwavelength anomalous dispersion MAD -nine-substituted protein. 

Hendrickson WA, Horton JR, LeMaster DM. Selenomethionyl proteins produced for analysis by multiwavelength anomalous diffraction (MAD) a vehicle for direct determination of three-dimensional structure. EMBO J... 

The prion protein, implicated in diseases such as mad cow and Creutzfeldt-Jakob, is another that has been proposed to undergo extensive refolding to form fibrils. In its native, cellular conformation (PrPc), residues 23-124 are... 

Bovine spongiform encephalopathy (BSE or mad cow disease) is a progressive neurological degenerative disease in cattle. It is caused by a mutated protein called a prion. BSE was first reported in the United Kingdom in 1986. Creutzfeldt-Jakob disease (CJD) is a rare disease that occurs in humans. Evidence to date indicates it is possible for humans to acquire CJD after consuming BSE-contaminated cattle products. 

Often the initial phases from one of the above techniques (particularly MIR and MAD) are not sufficiently accurate to build in all the atoms and further improvement of the phases must be carried out. The standard approach for this is called density modification, or solvent-flattening. The idea is that if a unit cell contains a sufficient amount of solvent in it (usually around 50%, which is reasonable for most protein crystals), you will be able to use this information to improve the phases for the protein. The region of the unit cell that contains the solvent is set to an average value and new structure factors and phases are then calculated for... 

The multiple-wavelength anomalous diffraction method (MAD) relies upon sufficiently strong anomalously scattering atoms in the protein structure itself In this method, diffraction data must be collected at a number of different wavelengths, usually requiring data collection with... 

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