Multi-domain proteins

Adaptor proteins are multi-domain proteins (Fig. 1) that interact with components of signaling pathways [1]. As a consequence of these interactions, adaptor proteins are able to regulate signaling events within the cell, providing spatiotemporal control and specificity, and influencing how a cell responds to a particular stimulus. 

The experimental approach used to mechanically stretch a chromatin fiber with the AFM is depicted schematically in Fig. 8a, and some example curves obtained with native chicken erythrocyte chromatin fibers are presented in Fig. 8b. These curves exhibited a saw-tooth pattern, similar to the patterns obtained upon stretching of multi-domain proteins like titin [71] or tenascin [72] (Fig. 8c). Each of... 

Gompounds that inhibit Akt-1 are of increasing interest as possible oncology therapeutics [59]. Akt-1 is a multi-domain protein that is known to be activated after binding of its pleckstrin homology (PH) domain to its endogenous target. A report from researchers at Merck indicates that their Akt-1 inhibitor does... 

Direct evidence for inter-domain dynamics in multi-domain proteins 136... 

RDC methods used to probe the structural dynamics between relatively large molecular fragments such as domains in multi-domain proteins can be... 

Mutations of the human APC gene are associated with both sporadic and familial forms of colon cancer. The APC protein is a large, multi-domain protein that has a 55-residue, N-terminal dimeric coiled coil (APC-55). Alber and colleagues used rules of thumb and those derived from an analysis of the covariation of a d and d d pairs in the cytokeratins (which form obligate heterodimers) to create a mutant of APC-55, anti-APCpl, as a potential probe for the APC protein (Sharma et al, 1998). 

Proapoptotic proteins can be further classified according to their BH domains (Figure 7.5). Some members, such as Bax and Bak, contain multiple domains and others, like Bid, Bad, Bim, and Bmf, contain only the BH3 domain (Gross et al., 1999 Kuwana and Newmeyer, 2003). These structural differences also reflect differences in their function. Multi-domain proteins directly induce outer mitochondrial membrane permeabi-... 

As a full-scale family classification system, more than 1200 MOTIFIND neural networks were implemented, one for each ProSite protein group. The training set for the neural networks consisted of both positive (ProSite family members) and negative (randomly selected non-members) sequences at a ratio of 1 to 2. ProClass groups non-redundant SwissProt and PIR protein sequence entries into families as defined collectively by PIR superfamilies and ProSite patterns. By joining global and motif similarities in a single classification scheme, ProClass helps to reveal domain and family relationships, and classify multi-domained proteins. 

Initial constructs are often designed based on previously solved crystal structures and usually contain only the catalytic kinase core. However, many kinases are multi-domain proteins and inclusion of additional domains can increase both protein stability and solubility. The minimal kinase domain typically contains five -strands and one a-helix in the N-terminal lobe and 7-8 a-helices in the C-termi-nal lobe. In tyrosine kinases, the N-terminal lobe usually starts near a highly conserved tryptophan, 14 residues upstream of the GxGxxG motif The start of the N-terminus is less well conserved in serine/threonine kinases. 

Blaschke, U. K., Cotton, G. J., and Muir, T. W. (2000) Synthesis of multi-domain proteins using expressed protein hgation Strategies for segmental isotopic labeling of internal regions. Tetrahedron 56, 9461-9470. 

Large multi-domain proteins require often molecular chaperones to fold properly. This is not considered in this review. 

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