Structural and Biochemical Analysis of Signal Transduction by the TRAF Family of Adapter Proteins
This extract was created in the absence of an abstract.
Excerpt
Cell-surface receptors utilize diverse strategies totransmit extracellular signals across the plasma membrane. Current major signaling paradigms include ligandpromoted conformational changes, cytoplasmic domainrearrangements, and oligomerization that directly juxtaposes cytoplasmic signaling modules. For the tumornecrosis factor (TNF) receptor superfamily, recent evidence supports a novel signaling mechanism. No conformational changes in the receptor traverse the membrane,and no direct receptor–receptor contacts are stabilized.Instead, the bound and free TNF superfamily receptorsappear to be distinguished by a geometric match betweenligand-stabilized receptor trimers and the proximal intracellular signal transducers, called TNF-receptor-associated factors (TRAFs). Here we review evidence supporting this emerging model, focusing on the X-ray structuresof the receptor-binding domain of TRAF2 bound to peptides derived from the cytoplasmic tails of CD40(McWhirter et al. 1999) and TNF receptor 2 (TNF-R2;Park et al. 1999). These structures, in conjunction withbiochemical data on TRAF oligomerization and receptorbinding, reveal the basis for receptor recognition and theinitiating events in signaling...
