Modular functional domains

B. SAGA HAT Complex Consists of Modular Functional Domains. 185... 

These are considered to be functionally competent protein domains owing to their ability to maintain their structure and molecular recognition properties independent of the full-length protein (Cohen GB, Ren R, Baltimore D. Modular binding domains in signal transduction proteins. Cell 1995 80 237-248). 

Considering the multitude of ubiquitin domains and their cognate recognition modules, the next question to address is how cells make use of these building blocks to form the highly complex ubiquitination system. Before starting with the discussion of some prominent modular protein architectures, we should bear in mind that there are a number of other functional domains participating in this... 

Steroid receptors contain multiple functional domains (Fig. 3) that are modular and whose sequences can be extensively conserved across the superfamily. Thus it is not surprising that there is considerable cross talk between and among members of the superfamily and their various shared partner proteins. As will be evident from Table 3, there is considerable overlap in the spectrum of enzymes regulated by nuclear receptors. Many examples exist wherein an individual nuclear receptor regulates multiple enzymes (16). 

Structural Insights, SH2 Domains An Example of Modular Regulatory Domains, takes a close look at phosphotyrosine-SH2 domain interactions and the diverse ways they can affect protein function. 

The RARs and RXRs, like other NRs, are comprised of a highly modular domain structure that includes autonomous DNA and ligand binding domains and as well as regions of the proteins that function in both transcriptional activation and silencing (Fig. 7.20). These functional domains are described in detail in the sections that follow. 

Like other transcriptional regulators, nuclear receptors exhibit a modular structure with different regions corresponding to autonomous functional domains. At the level of the primary structure the steroid hormone receptors can be divided into five different domains (Fig. 4.3), each with specific functions. 

Activators Are Modular Proteins Composed of Distinct Functional Domains... 

As with aggrecan, versican is a modular proteoglycan with multiple functional domains. Its core protein contains two terminal globular regions equivalent to the G1 and G3 regions of aggrecan separated by a large GAG-attachment domain... 

All NR proteins exhibit a characteristic modular structure that consists of five to six domains of homology (designated A-F, from the N-terminal to the C-terminal) based on regions of conserved sequence and function (Fig. 2). 

Peroxisome Proliferator-Activated Receptors. Figure 1 Common structural and functional features of nuclear receptor transcription factors. Consistent with other members of the nuclear receptor superfamily, the PPARs have a modular domain structure consisting of domains A/B, C, D, and E. Each domain is associated with specific functions. 

SHRs are built in a modular structure with similar structure elements. They contain a DNA-binding domain (DBD), a hinge region with a nuclear location signal (NLS), a ligand-binding domain (LBD) and several transcriptional activation functions (Fig. 1). 

Protein domains are the common currency of protein structure and function. Protein domains are discrete structural units that fold up to form a compact globular shape. Experiments on protein structure and function have been greatly aided by consideration of the modular nature of proteins. This has allowed very large proteins to be studied. The expression of individual domains has allowed the intractable giant muscle protein titin to be structurally studied (Pfuhl and Pastore, 1995). Protein domains can be found in a variety of contexts, (Fig. 1), in association with a range of unrelated domains and in a variety of orders. Ultimately protein domains are defined at the level of three-dimensional structure however, many protein domains have been described at the level of sequence. The success of sequence-based methods has been demonstrated by numerous confirmations, by elucidation of the three-dimensional structure of the domain. 

Although domains are often mobile and occur in many different modular architectures, it is notable that the co-occurrence of domains within single polypeptides is far from random, since a domain is usually found to co-occur only with a small subset of all domain types. When two domain types are not observed within the same molecule, it is likely that their activities are antagonistic, thereby effectively neutralizing the overall function of the molecule. Such an example is provided by protein kinase and phosphatase domains that are not currently known to cooccur within the same molecule. However, the reasons that functionally distinct and otherwise widespread domains have never yet been found together, such as signaling PDZ and SH2 domains, remains elusive. 

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