Loop-chain framework

The secondary structure elements, formed in this way and held together by the hydrophobic core, provide a rigid and stable framework. They exhibit relatively little flexibility with respect to each other, and they are the best-defined parts of protein structures determined by both x-ray and NMR techniques. Functional groups of the protein are attached to this framework, either directly by their side chains or, more frequently, in loop regions that connect sequentially adjacent secondary structure elements. We will now have a closer look at these structural elements. 

The residues not in the framework region form the loops between the p strands. These loops may vary in length and sequence among immunoglobulin chains of different classes but are constant within each class the sequence of the loops is invariant. The functions of these loops are not known, but they are probably involved in the effector functions of antibodies. When an antibody-antigen complex has been formed, signals are... 

The overall structure of the variable domain is very similar to that of the constant domain, hut there are nine p strands instead of seven. The two additional p strands are inserted into the loop region that connects p strands C and D (red in Figure 15.8). Functionally, this part of the polypeptide chain is important since it contains the hypervariahle region CDR2. The two extra p strands, called C and C", provide the framework that positions CDR2 close to the other two hypervariahle regions in the domain structure (Figure 15.8). 

The constant domain has a stable framework structure composed of two antiparallel sheets comprising seven p strands, four in one sheet and three in the other. The variable domains have a similar framework structure but comprising nine p strands, five in one sheet and four in the other. The three hypervariable regions are in loops at one end of the variable domain. The variable domains from the heavy and light chains associate through their five-stranded p sheets to form a barrel with the hypervariable loop regions from both domains close together at the top of the barrel. 

Figure 5 presents the N2 adsorption/desorption isotherms for calcined (650 °C) MSU-G silicas assembled from C H2 +,NH(CH2)2NH2 surfactants with n = 10, 12, and 14. The inset to the figure provides the framework pore distributions. The maxima in the Horvath-Kawazoe pore size distributions increase in the order 2.7, 3.2, 4.0 nm as the surfactant chain length increases. The textural porosity evident from the hysteresis loop at P/P0... 

In the heavy chain the first CDR of MOPC 315 has one more residue than in McPC 603. The Trp at position 353 was assigned to the interior corresponding to Met 34, a residue in the domain interior shown by other considerations (see below) to be structural, and the extra residue was placed in the exposed loop at the beginning of the first CDR, the Gly at position 32 permitting a sharp turn at the position. The second CDR of 315 is three residues shorter than McPC 603, and the third CDR is two residues shorter. These extra residues were excised and fitted onto the framework to give a first approximation of the model. Since the second and third CDR of Newm and 315 each have the same length, the orientations were adjusted to resemble Newm more closely. 

The antigens are colored pink parts of the antibody are colored as in Fig. 2.2. It can be seen that there is extensive binding to residues which formally belong to the framework, either in the dimer interface region for hapten binders or binders of peptides (which frequently use a side-chain in a hapten-like binding mode), and to the outer loop in protein binders. Hapten binders commonly form a deep, funnel-shaped binding pocket en-... 

The question sometimes arises as to why multiple frameworks are desirable in antibody Hbraries. There is a good reason why nature uses more than one framework in the antibody repertoire. As already mentioned above, antigens not only contact the CDRs, but also framework residues (Fig. 2.3). For example, large antigens make additional contact to the outer loop, or CDR4 mentioned above, while small haptens, but also side chains of peptide antigens, often bind in a deep cavity near the pseudo-2-fold axis of the antibody [15]. 

Somatic diversification of Vy regions does result from junctional variability (N segments and flexibility in recombination breakpoints), but, similarly to Va and Vp, is never observed after assembly. Thus, variability in y chains is likely to be topographically limited to the third CDR loop within a substantially conserved framework. 

It has long been recognized that proteins with similar amino acid sequences have similar three-dimensional protein structures. Differences between homologous structures usually occur in loops on the protein surface. The framework or core residues are conserved owing to constraints on the composition of interior side chains and other structural restraints. When a sequence is homologous to a protein of known structure, a knowledge-based approach to modeling is a very... 

Of course, this result established in the framework of the standard continuous model must remain true for any model, according to the universality principle. In particular, for a chain drawn on a lattice, the result (13.1.138) can easily be transcribed thus, we see that in this case, the probabilitity puN of forming a loop of N links, either at the end of the chain (i = 1) or in the middle of the chain (i = 2), is given by... 

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