Proteins modular structure

McGough, A.M., C.J. Staiger, J.K. Min, and K.D. Simonetti. 2003. The gelsolin family of actin regulatory proteins modular structures, versatile functions. FEBS Lett. 552 75-81. 

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). 

Bacitracin biosynthesis requires a non-ribosomal peptide synthetase with three major protein components, BacABC. This synthetase has a modular structure. There are associated regulatory and transport systems. Biosynthesis of bacitracin has been engineered in the surrogate host, B. subtilis, by genetic techniques. A strain, B. subtilis KE 350, expresses the entire 49-kb bacitracin... 

In many cases the various functions are located on independently folding protein domains, resulting in modularly constructed transcriptional activators. The function of a DNA-binding protein can thus often be deduced from the primary sequence information and from homology with other eucaryotic transcriptional activators. Furthermore, the modular structure of transcriptional activators is the prerequisite for the... 

Proteins have a modular structure comprised of motifs and domains. Short peptide sequences bring specificity for certain modifications while in most cases... 

The effects of DNA-binding transactivators on Pol II are mediated by coactivator protein complexes such as TFIID or mediator. The modular structures of the transactivators have distinct activation and DNA-binding domains. Other protein complexes, including histone acetyltransferases such as GCN5-ADA2-ADA3 and ATP-dependent complexes such as SWI/SNF and NURF, reversibly remodel chromatin structure. 

Fig. 1. Structure of spectrin superfamily proteins. Modular domains within each protein are clearly defined. Shaded spectrin repeats represent coiled coils involved in dimerization events incomplete repeats represent proportionally the number of coiled-coil helices contributed by a- and /3-spectrin when generating a complete spectrin repeat during formation of the spectrin tetramer. The dashed lines indicate how two spectrin heterodimers interact to form a functional spectrin tetramer. Asterisks in the dystrophin spectrin repeats represent the position of the two greater repeats in dystrophin with respect to utrophin, which in all other respects has a similar overall structure. Numbers in the EF hand regions represent the number of EF hand motifs.

However, the use of recombinant transcriptional activators (RTAs) appears to be the most generally applicable system at present. The construction of RTAs is based on the modular structure of transcription factors, which allows for the combination of DNA binding and transactivation domains derived from different proteins. For example, RTAs have been used to establish a positive feedback loop initiated by transcription from a weak cell type-specific promoter [94], Such... 

The two ERs share many functional characteristics based on their well conserved modular structure. As summarized above, AF-2 is responsible for estrogen-dependent activation through recruitment of coactivator proteins including members of the steroid receptor coactivator (SRC) family (Anzick et al., 1997 Chen et al., 1997 Hong et al., 1996 Kamei et al., 1996 Li et al., 1997 Onate et al., 1995 Torchia et al., 1997 Voegel et al., 1996). On the other hand, AF-1 activity is constitutive and ligand-independent (Berry et al., 1990 Kumar et al., 1987 Metzger et al., 1995). 

Figure 10.1 Domain and modular structure of 6-deoxyerythronolide B synthase (DEBS), the model modular PKS. ACP = acyl carrier protein ...

It has been observed that the use of protein tertiary structural class improved the accuracy for a 2-state secondary structure prediction (Kneller et al., 1990). A modular network architecture was proposed using separate networks (i.e., a- or P-type network) for classification of different secondary structures (Sasagawa Tajima, 1993). Recently, Chandonia Karplus (1995) trained a pair of neural networks to predict the protein secondary structure and the structural class respectively. Using predicted class information, the secondary structure prediction network realized a small increase in accuracy. 

Fig. 3.10. Modular structure of proteins of coagulation and thrombolysis. The shapes of structural motifs, their amino (N) and carboxyl termini (C) and the stabilizing disulfide bridges (bars) are shown on the top. Shown below each module is the schematic symbol used to represent them in the proteins shown.

Figure 15.11. Modular Structure of Phospholipase C. The domain structures of three isoforms of phospholipase C reveal similarities and differences among the isoforms. Only the P isoform, with the G-protein-binding domain, can be stimulated directly by G proteins. For phospholipase Cy, the insertion of two SH2 (Src homology 2) domains and one SH3 (Src homology 3) domain splits the catalytic domain and a PH domain into two parts.

This process takes place outside the cell. Dimerization of the extracellular domains of the receptor brings together the intracellular domains as well. Associated with each intracellular domain is a molecule of a protein kinase termed Janus kinase 2 (JAK2) in an unactivated form. Janus kinases have modular structures consisting of four previously described domains (Figure 15.26). 

Present-day structures of proteins provide some hints on the role of gene duplications in evolution. Proteins commonly occur in families. These are structurally related enzymes catalyzing reactions of the same class with different substrate specificities. Examples are families of proteases or dehydrogenases. In addition to this, one observes interesting regularities in the structures of many globular proteins Substructures (so-called motifs) are often repeated exactly or with minor modifications only. Such repetitions were found in the same protein molecule as well as in different protein molecules. Both the modular structure of polymers as well as the existence of protein families can be explained by a gene duplication mechanism. 

Figure 14.21 The modular structure of Insulin receptor substrates IRS-1 and IRS-2 This schematic view represents the amino acid sequence common to IRS-1 and lRS-2. Each protein contains a pleckstrin homology domain (which binds phosphoinositide lipids), a phospbotyrosine-binding domain, and four sequences that approximate Tyr-X-X-Met (YXXM). The latter are phosphorylated by the insulin receptor tyrosine kinase.

The catalytic subunit of PPl is a 37 kd single-domain protein. This subunit is usually bound to one of a family of regulatory subunits with masses ol approximately 120 kd in skeletal muscle and heart, the most prevalent regulatory subunit is called Gvr. whereas, in the liver, the most prevalent subunit is Gl. These regulatory subunits have modular structures with domains that participate in interactions with glycogen, with the catalytic subunit, and... 

Although the specificity of the CBMs binding polysaccharides is the same as the catalytic domain more often than not, there are many examples to the contrary from enzymes hydrolysing the plant cell wall. Thus, an acetylxylan esterase Cellvibrio japonicus ioxm.Qx y P.fluorescens subsp. cellulosa) contains a cellulose binding domain. Moreover the modular structure permits fairly complicated proteins to be built up one chitinase, for example, from a hyperthermophilic archeon, had two GH 18 catalytic domains and two Family 1 and a Family 5 CBMs. °... 

Like transcription factors, most hnRNP proteins have a modular structure. They contain one or more RNA-binding domains and at least one other domain that is thought to interact with other proteins. Several different RNA-binding motifs have been Identified by constructing deletions of hnRNP proteins and testing their ability to bind RNA. 

---