Large polypeptide chains

Large polypeptide chains fold into several domains... 

Figure 12.5 Proteolytic cleavage of prothrombin by factor Xa, yielding active thrombin. Although prothrombin is a single-chain glycoprotein, thrombin consists of two polypeptides linked by what was originally the prothrombin intrachain disulfide bond. The smaller thrombin polypeptide fragment consists of 49 amino acid residues, and the large polypeptide chain contains 259 amino acids. The N-terminal fragment released from prothrombin contains 274 amino acid residues. Activation of prothrombin by Xa does not occur in free solution, but at the site of vascular damage...

The folding pathway of a large polypeptide chain is unquestionably complicated, and not all the principles that guide the process have been worked out. However, extensive study has led to the development of several... 

Although the basic biochemical reactions in fatty acid synthesis are very similar in E. coli and eukaryotes, the structure of the synthase varies considerably. The fatty acid synthases of eukaryotes, in contrast with those of E. coli, have the component enzymes linked in a large polypeptide chain. 

Immunoglobulins all have a similar structure each antibody molecule contains two identical small polypeptide chains (the light or L chains) and two identical large polypeptide chains (the heavy or H chains) (Fig. 7.16). The chains are joined to each other by disulfide bonds. 

Since each dipeptide has a —GOOH and an —NH, group, a tripeptide can be formed from each dipeptide by reaction at either end, and the polymerization process can continue until a large polypeptide chain is formed (Figure 15.9). Note that, as above, peptides are always written with the N-terminal end at the left. 

Proteins consist essentially of one or more large polypeptides chains. The first solid-state NMR spectra of proteins were reported in 1991 by Oldfield and co-workers [13], which successfully acquired static powder spectra of a 67 kDa tetramer [ O2]haemoglobin and a 17 kDa [ 02]myo-globin sample. In 1998, the same team [13] recorded MAS NMR spectra of [ 02] myoglobin at 11.7 T, from which a Cq of less than 2 MHz was derived. Unfortunately, no further studies were published until 2010, thanks to the advanced NMR instrumentation and methodology, Wu and co-workers [37] reported a MAS NMR study at 21.14 T of two protein-ligand complexes, the egg-white avidin-[ 02]biotin (64 kDa) and... 

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

These events marked the beginning of the Ig domain unfolding, after which the strands unraveled one at a time, accompanied by a large reduction in the recorded force. After an extension of 260 A, the domain was completely unfolded further stretching of the already extended polypeptide chain caused the force to increase dramatically. 

Human growth hormone is a single polypeptide chain of 191 amino acids (qv) having two disulfide bonds, one between Cys-53 and Cys-165, forming a large loop in the molecule, and the other between Cys-182 and Cys-189, forming a small loop near the C-terminus. The stmcture of hGH is shown in Figure 1 molecular mass is 22,125 the empirical formula is C qH 29N 262 300 7 ... 

Protein molecules that have only one chain are called monomeric proteins. But a fairly large number of proteins have a quaternary structure, which consists of several identical polypeptide chains (subunits) that associate into a multimeric molecule in a specific way. These subunits can function either independently of each other or cooperatively so that the function of one subunit is dependent on the functional state of other subunits. Other protein molecules are assembled from several different subunits with different functions for example, RNA polymerase from E. coli contains five different polypeptide chains. 

Figure 3.6 Four-helix bundles frequently occur as domains in a proteins. The arrangement of the a helices is such that adjacent helices in the amino acid sequence are also adjacent in the three-dimensional structure. Some side chains from all four helices are buried in the middle of the bundle, where they form a hydrophobic core, (a) Schematic representation of the path of the polypeptide chain in a four-helrx-bundle domain. Red cylinders are a helices, (b) Schematic view of a projection down the bundle axis. Large circles represent the main chain of the a helices small circles are side chains. Green circles are the buried hydrophobic side chains red circles are side chains that are exposed on the surface of the bundle, which are mainly hydrophilic.

Figure 8.21 Richardson-type diagram of the structure of one suhunit of the lac repressor. The polypeptide chain is arranged in four domains, an amino terminal DNA-hinding domain (red) with a helix-tum-helix motif, a hinge helix (purple), a large core domain which has two subdomains (green and hlue) and a C-terminal a helix. (Adapted from M. Lewis et al.. Science 271 1247-1254, 1996.)...

The polypeptide chain of the lac repressor subunit is arranged in four domains (Figure 8.21) an N-terminal DNA-hinding domain with a helix-turn-helix motif, a hinge helix which binds to the minor groove of DNA, a large core domain which binds the corepressor and has a structure very similar to the periplasmic arablnose-binding protein described in Chapter 4, and finally a C-terminal a helix which is involved in tetramerization. This a helix is absent in the PurR subunit structure otherwise their structures are very similar. 

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