Proteins containing the PB1 domain, a protein interaction module conserved in animals, fungi, amoebas, and plants, participate in diverse biological processes. The PB1 domains adopt a ubiquitin-like beta-grasp fold, containing two alpha helices and a mixed five-stranded beta sheet, and are classified into groups harboring an acidic OPCA motif (type I), the invariant lysine residue on the first beta strand (type II), or both (type I/II). The OPCA motif of a type I PB1 domain forms salt bridges with basic residues, especially the conserved lysine, of a type II PB1 domain, thereby mediating a specific PB1-PB1 heterodimerization, whereas additional contacts contribute to high affinity and specificity of the modular interaction. The canonical PB1 dimerization is required for the formation of complexes between p40(phox) and p67(phox) (for activation of the NADPH oxidase crucial for mammalian host defense), between the scaffold Bem1 and the guanine nucleotide exchange factor Cdc24 (for polarity establishment in yeasts), and between the polarity protein Par6 and atypical protein kinase C (for cell polarization in animal cells), as well as for the interaction between the mitogen-activated protein kinase kinase kinases MEKK2 or MEKK3 and the downstream target mitogen-activated protein kinase kinase MEK5 (for early cardiovascular development in mammals). PB1 domains can also mediate interactions with other protein domains. For example, an intramolecular interaction between the PB1 and PX domains of p40(phox) regulates phagosomal targeting of the microbicidal NADPH oxidase; the PB1 domain of MEK5 is likely responsible for binding to the downstream kinase ERK5, which lacks a PB1 domain; and the scaffold protein Nbr1 associates through a PB1-containing region with titin, a sarcomere protein without a PB1 domain. This Review describes various aspects of PB1 domains at the molecular and cellular levels.
|Science's STKE : signal transduction knowledge environment
|Published - Aug 28 2007
All Science Journal Classification (ASJC) codes
- General Medicine