In presence of glucocorticoids

Glucocorticoid

Glucocorticoid receptor complex, unoccupied

I Cytoplasmic activation

Complex

FIGURE 10-21 Anti-inflammatory action of glucocorticoid mediated by the direct interaction of N'FkB p65 and the glucocorticoid receptor.

SIR*

I Cytoplasmic activation

Complex

Reduced inflammation

FIGURE 10-21 Anti-inflammatory action of glucocorticoid mediated by the direct interaction of N'FkB p65 and the glucocorticoid receptor.

tions and the significance of amino acid residues are specified.

Downstream from the Zn2+ finger a basic region is encountered, which serves as the nuclear localization signal. The amino acid sequences that comprise this signal among several receptors of this family are shown in Figure 10-24. These sequences are bound by specific cytoplasmic proteins, called the nucleoporin family, which are presumed to dock the cytoplasmic receptor within the structure of the nucleopore (Figure 10-15) for transport into the nucleus. Other proteins may be involved in the transport process, and hsp 70 and aG protein (RAN) have been suggested to participate, hsp 70 could contribute energy to the process by its

ATPase activity. The transporting family of cytoplasmic proteins was discovered in an interesting way. Some Japanese researchers took the SV40 T antigen sequence of the nuclear localization signal, KKKRK, and decided to prepare a "mirror image" peptide in which K's were replaced by aspartates (D) and R was replaced by glutamate (E), generating the peptide DDDED. This sequence was synthesized and an antibody was prepared against DDDED. The antibody cross-reacted with the SV40 T antigen nuclear localization signal and also with a 69-kDa protein, which was found to bind to the nuclear localization signal. These cytoplasmic proteins constitute a family of proteins that are involved in nuclear transport.

FIGURE 10-22 Mode of binding of steroid receptor to inverted repeats (P3) versus the binding of the vitamin D receptor to direct repeats (DR3). The orientation of the recognition element in the major groove is implied by the arrows of the DBD. The symmetrical dimerization region of the steroid receptor DBDs is indicated by white ovals, whereas the heterologous dimerization region of vitamin D is indicated by black and white ovals. Like the vitamin D receptor, other nuclear receptors that bind to direct repeats may form analogous heterologous associations. The hormone-binding domain, which has a stronger dimerization function, may form a symmetrical dimerization interface. The two domains may be linked by a flexible tether. Reproduced with permission from Luisi, B. F., Schwabe, J. W. R., and Freedman, L. P. (1994). The steroid/nuclear receptors: From three-dimensional structure to complex formation". Vitam. Horm. 49, 1-48.

Cure Tennis Elbow Without Surgery

Cure Tennis Elbow Without Surgery

Everything you wanted to know about. How To Cure Tennis Elbow. Are you an athlete who suffers from tennis elbow? Contrary to popular opinion, most people who suffer from tennis elbow do not even play tennis. They get this condition, which is a torn tendon in the elbow, from the strain of using the same motions with the arm, repeatedly. If you have tennis elbow, you understand how the pain can disrupt your day.

Get My Free Ebook


Post a comment