Invariant sequence

Zinc-finger proteins are also possible targets for bicyclams. All nu-cleocapsid proteins of known strains of retroviruses contain one or two copies of an invariant sequence, Cys-X2-Cys-X4-His-X4-Cys. Proteins with this sequence bind zinc stoichiometrically with dissociation constants of ca. 10-12M (377). Under physiological conditions, a 10-fold excess of EDTA removes only 50% of zinc from the zinc finger domain of HIV-1 nucleocapsid protein (378). 

Biswas, R Jiang, X. Pacchia, A. L. Dougherty, J. R Peltz, S. W. The human immunodeficiency virus type 1 ribosomal frameshifting site is an invariant sequence determinant and an important target for antiviral therapy. J. Virol. 2004, 78, 2082-2087. 

Complete sequences of ca. 50 different plant-type ferredoxins(Fd) are known. The invariant sequences nearest to the 2-Fe core are confirmed to be Pro-Tyr-Ser-Cys-Arg-Ala-Gly-Ala-Cys-Ser-Thr-Cys-Ala-Gly and Leu-Thr-Cys-Val. 2Fe-2S complexes of oligopeptides with the Cys-X-Y-Cys sequence have been synthesized by ligand exchange reactions (7,23). We have examined the redox potentials of these model complexes, and the results are shown in Table I. The reversibility improved remarkably and the potential approached the value of the native proteins as the sequence more closely simulated that of the proteins. It is conjectured that hydrogen bonds from the peptide N-H s to thiolate and/or sulfide groups increase the stability of the reduced cluster. It is likely that peptide sequences like those found in the proteins favor the formation of such hydrogen bonds. 

The Na+,K+- ATPase is one of a family of over 50 ion pumps that are characterized by transfer of a phospho group from ATP to an aspartate side chain carboxylate in the invariant sequence DKTG to give an intermediate phosphoenzyme + aDP.530 537... 

After the U1 snRNP binds to the pre-mRNA (step a, Fig. 28-22)614 the U2 snRNP binds to another almost invariant sequence CURACU found 20 to 55 nucleotides upstream of the 3 junction.608,615-617 The A in this sequence becomes a branch point. It is brought close to the 5 splice site with the aid of a preassembled complex of snRNPs U4, U6, and U5. In this complex U4 and U6 are tightly paired, additional proteins are also present,618 21 and enhancers may be located in adjacent exons.617 Upon binding of U6 to the 5 splice site, the U1 and U4 snRNPs are released (step b, Fig. 28-22) and the 2 -OH of the branch point adenosine attacks the backbone phosphorus atom (step c) at the 5 splice junction forming a lariat intermediate. The 3 end created at the 5 junction must now be held and brought close to the 3 splice junction, which is located with the aid of U5 snRNP.622 The 3 splice junction, utilized in the second splicing step (step d, Fig. 28-22) has the consensus sequence (T/C)N(C/T)AG G. 

Since the protein environment around the iron site of the iron sulfur protein is related to the protein s biological function, peptide sequences nearest to the iron core are of utmost importance. Based on the peptide sequences reported for various iron-sulfur proteins, some examples of invariant sequences are discernible. For example, Cys-Gly-X-Cys sequences are involved in coordination at the active sites of bacterial ferredoxins (9). This macro-ring chelation is believed to be a feature and conveys specific chemical properties to the iron core. 

The structure of oxidized Spirulina platensis ferredoxin has been established by X-ray analysis, and is as shown in Fig. 9 (30). Three Cys thiolates in an invariant sequence, Cys-A-B-C-D-Cys-X-Y-Cys, bind the... 

The synthetic [2Fe-2S] model complex of the 20-peptide complex exhibits two LMCT absorption maxima at 423 and 461 nm in DMF, maxima which are near to those of the native plant-type ferredoxin (423 and 466 nm) (69). Two redox couples for — 3/—2 were observed at — 0.64 V versus SCE and at —0.96 V versus SCE in DMF. One of them is very close to the value (—0.64 V versus SCE) of native ferredoxin. The 20-peptide complex containing invariant sequences Cys-A-B-C-D-Cys-X-Y-Cys and Leu-Thr-Cys-Val possesses all essential factors for a model of the active site except for the peptide conformation. The positive-shifted redox potential of the 20-peptide complex in DMF is undoubtedly due to the interactions between the Fe2S22+ core and adjacent amino-acid residues, giving rise to NH--S hydrogen bonding. 

Stable polymorphic modifications are possible usually in systems distinguished by directionality, which in polyamides is caused by steric polarity resulting from the invariable sequence of the CONH groups. As is shown schematically in Figure 2.25, steric polarity is absent in polyamides of the X,Y-type but is a distinct characteristic of the Z-type polyamides. 

This is the building block which is particularly important in all habits and repeated invariant sequences of behaviour. The sequences are built up by a process called conditioning. This has three essential elements ... 

The H chain of human IgG consists of four domains (Fig. 1.3) including an N-terminal, Vh domain, with approximately 115 amino acid residues and three domains of invariant sequence (ChI, Ch2, and Ch3 C for constant ). All the domains are roughly equal in size, and each domain has the characteristic intrachain disulfide loop. It has been suggested that each domain may have one or more particular biological functions. For example, the V domain provides for antibody specificity, and the Ch2 domain is associated with complement fixation. 

The term invariant sequence applies to members of the same class and subclass, for example the IgGl subclass of IgG. Within a subclass there may be minor, genetically determined differences in the... 

In the 12 complete sequences shown in Fig. 4.14, 25 positions are invariant. Many of these residues are also correspondingly located and invariant in the Vh regions of mouse, rabbit, and guinea pig immunoglobulins. In the human proteins these include the 2 half-cystines, Trp 38 and 49,5 of 7 amino acids in positions 92-98, and positions 120, 122, and 123, which are at the junction of the V and C regions. (IgM becomes clearly distinguishable from IgG at position 124 and thereafter.) This relatively invariant sequence at the V/C junction is also con-... 

---