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1.
Two types of distributions for the frequencies of occurrence of amino acids in each position of hypervariable regions CDR-1 and CDR-2 were obtained for 2,000 immunoglobulins. The results show that some positions fit an inverse power-law distribution, while others fit an exponential-type distribution. As a result of comparison with structural data in the literature it is proposed that sites in which the frequency distribution fits the inverse power law are critical to maintaining canonical shapes of the recognition regions or are involved in modulating these canonical conformations, while those sites where the distribution fits the exponential law are those which should be exclusively involved in the recognition mechanism.
Correspondence to: F. Lara-Ochoa 相似文献
2.
Aligning,analyzing, and visualizing sequences for antibody engineering: Automated recognition of immunoglobulin variable region features 下载免费PDF全文
The analysis and comparison of large numbers of immunoglobulin (Ig) sequences that arise during an antibody selection campaign can be time‐consuming and tedious. Typically, the identification and annotation of framework as well as complementarity‐determining regions (CDRs) is based on multiple sequence alignments using standardized numbering schemes, which allow identification of equivalent residues among different family members but often necessitate expert knowledge and manual intervention. Moreover, due to the enormous length variability of some CDRs the benefit of conventional Ig numbering schemes is limited and the calculation of correct sequence alignments can become challenging. Whereas, in principle, a well established set of rules permits the assignment of CDRs from the amino acid sequence alone, no currently available sequence alignment editor provides an algorithm to annotate new Ig sequences accordingly. Here we present a unique pattern matching method implemented into our recently developed ANTIC ALIgN editor that automatically identifies all hypervariable and framework regions in experimentally elucidated antibody sequences using so‐called “regular expressions.” By combination of this widely supported software syntax with the unique capabilities of real‐time aligning, editing and analyzing extended sets of amino acid and/or nucleotide sequences simultaneously on a local workstation, ANTIC ALIgN provides a powerful utility for antibody engineering. Proteins 2016; 85:65–71. © 2016 Wiley Periodicals, Inc. 相似文献
3.
Predicting antibody hypervariable loop conformations. II: Minimization and molecular dynamics studies of MCPC603 from many randomly generated loop conformations 总被引:14,自引:0,他引:14
We describe a method for predicting the conformations of loops in proteins and its application to four of the complementarity determining regions [CDRs] in the crystallographically determined structure of MCPC603. The method is based on the generation of a large number of randomly generated conformations for the backbone of the loop being studied, followed by either minimization or molecular dynamics followed by minimization starting from these random structures. The details of the algorithm for the generation of the loops are presented in the first paper in this series (Shenkin et al. [submitted]). The results of minimization and molecular dynamics applied to these loops is presented here. For the two shortest CDRs studied (H1 and L2, which are five and seven amino acids long), minimizations and dynamics simulations which ignore interactions of the loop amino acids beyond the carbon beta replicate the conformation of the crystal structure closely. This suggests that these loops fold independently of sequence variation. For the third CDR (L3, which is nine amino acids), those portions of the CDR near its base which are hydrogen bonded to framework are well replicated by our procedures, but the top of the loop shows significant conformational variability. This variability persists when side chain interactions for the MCPC603 sequence are included. For a fourth CDR (H3, which is 11 amino acids long), new low-energy backbone conformations are found; however, only those which are close to the crystal are compatible with the sequence when side chain interactions are taken into account. Results from minimization and dynamics on single CDRs with all other CDRs removed are presented. These allow us to explore the extent to which individual CDR conformations are determined by interactions with framework only. 相似文献
4.
The V-region sequence of the H chain from a third rabbit anti-pneumococcal antibody. 总被引:2,自引:0,他引:2 下载免费PDF全文
J C Jaton 《The Biochemical journal》1976,157(2):449-459
The amino acid sequence of the V (variable) region of the heavy (H) chain of rabbit antibody BS-1, raised against type III pneumococcal vaccine, is reported. Together with the sequence data of the V region of the light (L) chain previously determined [Jaton (1974a) Biochem. J. 141, 1-13], the present work completes the analysis of the V domain of the homogeneous antibody BS-1. The V domains (VL + VH regions) of this antibody are compared with those of two other anti-(type III) pneumococcal antibodies BS-5 and K-25 [Jaton (1975) Biochem. J. 147, 235-247]. Except for the second hypervariable section of the L chains, these antibodies have very different sequences in the hypervariable segments of the V domains. Within the third hypervariable region of the H chain, each antibody has a different length: BS-1 is three amino acids shorter than K-25 and two amino acids shorter than BS-5. When the sequences in that section are aligned for maximal homology, only two residues, glycine-97 and leucine-101, are common to the three antibodies. On the basis of the amino acid sequences of these three anti-pneumococcal antibodies, the results do not support the concept of a simple correlation between primary structure in the hypervariable sections (known to determine the shape of the combining site) and antigen-binding specificity. 相似文献
5.
Forty-six immunoglobulin VH gene sequences of rainbow trout were compiled to analyze the extent of variations and the frequency of nucleotide changes
in CDRs and FRs. The results show that the frequency of nonsynonymous (amino acid replacing) changes (Ka) are on average 4.9
times higher in complementarity determining regions (CDRs) than in FRs, thus contributing more diversity in CDRs. Unexpectedly,
however, the frequency of synonymous (silent) changes (Ks) show the same tendency: it was 5.3 times higher in CDRs than in
framework regions (FRs). The distribution of Ks/Ka ratios of each comparison shows no segregation between CDRs and FRs. The
same analysis applied to five germline VH genes of Heterodontus francisci shows the same result as was found with the rainbow trout. In contrast, the results from mouse data show that, while the
CDR/FR ratio for Ka is much higher (7.4), the CDR/FR ratio for Ks is only slightly higher (1.8). The distribution of Ks/Ka
ratios in mouse indicates clear segregation between CDRs and FRs. This suggests that CDR germline diversity is largely generated
by gene conversion in VHs of lower vertebrates such as rainbow trout or shark. This mechanism might be advantageous to lower vertebrates in generating
V gene diversity faster than other mechanisms such as point mutation and selection.
Received: 10 July 1996 / Revised: 9 September 1996 相似文献
6.
Simon PJ Brogle KC Wang B Kyle DJ Soltis DA 《Archives of biochemistry and biophysics》2005,440(2):148-157
Peptide display in antibody complementarity determining regions (CDRs) offers several advantages over other peptide display systems including the potential to graft heterologous peptide sequences into multiple positions in the same backbone molecule. Despite the presence of six CDRs in an antibody variable domain, the majority of insertions reported have been made in heavy chain CDR3 (h-CDR3) which may be explained in part by the highly variable length and sequence diversity found in h-CDR3 in native antibodies. The ability to graft peptide sequences into CDRs is restricted by amino acids in these loops that make structural contacts to framework regions or are oriented towards the hydrophobic interior and are important for the proper folding of the antibody. To identify such positions in human kappa-light chain CDR1 (kappa-CDR1) and CDR2 (kappa-CDR2), we performed alignments of 1330 kappa-light chain variable region amino acid sequences and 19 variable region X-ray crystal structures. From analyses of these alignments, we predict insertion points where sequences can be grafted into kappa-CDR1 and kappa-CDR2 to prepare synthetic antibody molecules. We then tested these predictions by inserting somatostatin and somatostatin-related sequences into kappa-CDR1 and kappa-CDR2, and analyzing the expression and ability of the modified antibodies to bind to membranes containing somatostatin receptor 5. These results expand the repertoire of CDRs that can be used for the display of heterologous peptides in the CDRs of antibodies. 相似文献
7.
The prion diseases, such as Creutzfeldt-Jakob disease of humans and bovine spongiform encephalopathy, involve the aberrant
metabolism and accumulation of prion protein PrP. There are three contradictory hypotheses about evolution of prion protein
gene PRNP. Population genetic studies have proposed that PRNP could be under balancing selection, strong purifying selection, or mainly positive selection. We made use of the maximum
likelihood tests for detection of positive selection at the amino acid level and present availability of PRNP coding sequences to contribute to these disagreements. Positive selection could occur at amino acids residing in active sites,
and at amino acids involved in protein-protein interactions. Thus we tested a hypothesis that positive selection at the amino
acid level in PrP might have taken place in human and related species from the superordinal group Euarchonta, as well as in
bovine and related species from the superordinal clade Laurasiatheria. Our study and the present experimental evidences indicate
that positive selection at the amino acid level might have taken place in the PrP signal sequences and conformationally plastic
PrP regions, as well as at the protein X binding sites.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Prof. Vera Gamulin passed away. 相似文献
8.
K. Ushijima H. Sassa R. Tao H. Yamane A. M. Dandekar T. M. Gradziel H. Hirano 《Molecular & general genetics : MGG》1998,260(2-3):261-268
cDNAs encoding three S-RNases of almond (Prunus dulcis), which belongs to the family Rosaceae, were cloned and sequenced. The comparison of amino acid sequences between the S-RNases
of almond and those of other rosaceous species showed that the amino acid sequences of the rosaceous S-RNases are highly divergent,
and intra-subfamilial similarities are higher than inter-subfamilial similarities. Twelve amino acid sequences of the rosaceous
S-RNases were aligned to characterize their primary structural features. In spite of␣their high level of diversification,
the rosaceous S-RNases were found to have five conserved regions, C1, C2, C3, C5, and RC4 which is Rosaceae-specific conserved
region. Many variable sites fall into one region, named RHV. RHV is located at a similar position to that of the hypervariable
region a (HVa) of the solanaceous S-RNases, and is assumed to be involved in recognizing S-specificity of pollen. On the other hand, the region corresponding to another solanaceous hypervariable region (HVb) was
not variable in the rosaceous S-RNases. In the phylogenetic tree of the T2/S type RNase, the rosaceous S-RNase fall into two
subfamily-specific groups (Amygdaloideae and Maloideae). The results of sequence comparisons and phylogenetic analysis imply
that the present S-RNases of Rosaceae have diverged again relatively recently, after the divergence of subfamilies.
Received: 28 May 1998 / Accepted: 13 August 1998 相似文献
9.
Yoshiki Fujii Takaji Matsutani Kazutaka Kitaura Satsuki Suzuki Tsunetoshi Itoh Tomohiko Takasaki Ryuji Suzuki Ichiro Kurane 《Immunogenetics》2010,62(6):383-395
The common marmoset (Callithrix jacchus) is useful as a nonhuman primate model of human diseases. Although the marmoset model has great potential for studying autoimmune
diseases and immune responses against pathogens, little information is available regarding the genes involved in adaptive
immunity. Here, we identified one TCR α constant (TRAC), 46 TRAJ (joining), and 35 TRAV (variable) segments from marmoset
cDNA. Marmoset TRAC, TRAJ, and TRAV shared 80%, 68–100%, and 79–98% identity with their human counterparts at the amino acid
level, respectively. The amino acid sequences were less conserved in TRAC than in TCRβ chain constant (TRBC). Comparative
analysis of TRAV between marmosets and humans showed that the rates of synonymous substitutions per site (d
S
) were not significantly different between the framework regions (FRs) and complementarity determining regions (CDRs), whereas
the rates of nonsynonymous substitutions per site (d
N
) were significantly lower in the FRs than in CDRs. Interestingly, the d
N
values of the CDRs were greater for TRBV than TRAV. These results suggested that after the divergence of Catarrhini from Platyrrhini, amino acid substitutions were decreased in the FRs by purifying selection and occurred more frequently in CDRβ than in CDRα
by positive selection, probably depending on structural and functional constraints. This study provides not only useful information
facilitating the investigation of adaptive immunity using the marmoset model but also new insight into the molecular evolution
of the TCR heterodimer in primate species. 相似文献
10.
Analysis of the interaction between the bacterial superantigen streptococcal pyrogenic exotoxin A (SpeA) and the human T-cell receptor 总被引:2,自引:0,他引:2
Streptococcus pyogenes that produces the bacterial superantigen streptococcal pyrogenic exotoxin A (SpeA) is associated with outbreaks of streptococcal toxic shock syndrome (STSS) in the United States and Europe. SpeA stimulates Vβ2.1, 12.2, 14.1, and 15.1-positive T cells, and the lymphokine production from the activated T cells is believed to result in the symptoms associated with STSS. The T-cell receptor (TCR)–SpeA interaction is crucial for superantigenic activity, and studies were undertaken to determine regions of both SpeA and the TCR involved in the formation of MHC/SpeA/TCR complexes. Previously, recombinant toxins encoded by speA alleles 1, 2, and 3 as well as toxins resulting from 19 distinct point mutations in speA1 were generated. Here, these 22 toxin forms were incubated with human peripheral blood mono- nuclear cells (PBMCs), and the percentages of T-cell blasts bearing Vβ chains 2.1, 12.2, and 14.1 were quantified by flow cytometry. The analysis indicates that the residues of SpeA needed for a productive TCR interaction differ for each Vβ chain examined. An amino acid substitution at only one site significantly affected the toxin’s ability to stimulate Vβ2.1-expressing T cells, three individual amino acid substitutions resulted in significant loss of ability to stimulate Vβ12.2-expressing T cells, and substitution at 13 individual sites significantly affected the ability to stimulate Vβ14.1-expressing T cells. To elucidate the regions of the Vβ chains that interacted with SpeA, synthetic peptides representative of the human Vβ12.2 complementary-determining regions (CDRs) 1, 2, and 4 were used to block the SpeA-mediated proliferation of human PBMCs. The CDR1, CDR2 and CDR4 peptides were each able to block proliferation, with the activity of CDR1 > CDR2 > CDR4. Combinations of CDR1 peptide with CDR2 or CDR4 peptides allosterically enhanced the ability of each to block proliferation, suggesting SpeA has distinct binding sites for the CDR loops. 相似文献
11.
Six dichloro-s-triazine (DCT) reagents having l-Leu, d-Phg, l-Val, l-Met, l-Ala and l-Met-NH2 as chiral auxiliaries in cyanuric chloride were introduced for enantioseparation of 13 proteinogenic amino acids. Four other
DCTs and six monochloro-s-triazine (MCT) reagents having amino acid amides as chiral auxiliaries were also synthesized. These 16 chiral derivatizing
reagents (CDRs) were used for synthesis of diastereomers of all the 13 analytes using microwave irradiation, which were resolved
by reversed-phase high-performance liquid chromatography (RP-HPLC) using C18 column and gradient eluting mixture of aqueous
TFA and acetonitrile with UV detection at 230 nm. It required only 60–90 s for derivatization using microwave irradiation.
Better resolution and lower retention times were observed for the diastereomers prepared with CDRs having amino acids as chiral
auxiliaries as compared to counterparts prepared with reagents having amino acid amides as chiral auxiliaries. As the best
resolution of all the 13 analytes was observed for their diastereomers prepared using the DCT reagent having l-Leu as chiral auxiliary, this CDR was further employed for derivatization of Lys, Tyr, His and Arg followed by RP-HPLC analysis
of resulting diastereomers. The results are discussed in light of acid and amide groups of chiral auxiliaries constituting
CDRs, electronegativities of the atoms of achiral moieties constituting CDRs and hydrophobicities of side chains of amino
acids constituting CDRs and analytes. 相似文献
12.
Comparison of the amino acid sequences of the variable domains of two homogeneous rabbit antibodies to type III pneumococcal polysaccharide. 下载免费PDF全文
J C Jaton 《The Biochemical journal》1975,147(2):235-247
The amino acid sequences of the V (variable) regions of the H (heavy) and L (light) chains derived from rabbit antibody K-25, specific for type III pneumococci, were determined; this is the second homogeneous rabbit antibody besides antibody BS-5 whose complete sequence of the V domain has been established (Jaton, 1974d). The V regions of L chains BS-5 and K-25 (both of allotype b4) differ from each other by 19 amino acid residues; 11 of these 19 substitutions are located within the three hypervariable sections of the V region. On the basis of seven amino acid differences within the N-terminal 28 positions, it is suggested that L chain K-25 belongs to a different subgroup of rabbit K chains and L chain BS-5. H chain K-25 (allotype a2) differs from another H chain of the same allotype by one amino acid substitution within the N-terminal 70 positions in addition to interchanges occurring in the first two hypervariable sections. H chain K-25 was compared with H chain BS-5 (allotype a1) and with the known V-region rabbit sequences. Allotype-related differences between a1, a2 and a3 chains appear to occur within the N-terminal 16 positions and possibly in scattered positions throughout the V-region. In the hypervariable positions, variability between the two antibodies is remarkably more pronounced within the third hypervariable section of both H and L chains than within the first two. 相似文献
13.
《Bioscience, biotechnology, and biochemistry》2013,77(10):2460-2466
In the detergent industry, fungal endoglucanases are used to release microfibrils from the surfaces of dyed cellulosic fabrics to enhance color brightness. Family 45 endoglucanase (glycoside hydrolase family 45, GH45) EGL3 from Humicola grisea is more resistant to anionic surfactants and oxidizing agents than family 45 endoglucanase RCE1 from Rhizopus oryzae, while in the present study, a catalytic domain of RCE1 had higher defibrillation activity on dyed cotton fabrics than did that of EGL3. To identify the amino acid regions involved in these properties, we compared the characteristics of RCE1, EGL3, and three chimeric endoglucanases, in which each of the three regions of the catalytic domain of EGL3 was replaced by the corresponding region of the catalytic domain of RCE1. Amino acids in the N-terminal region were involved in resistance to anionic surfactants and oxidizing agents. Furthermore, amino acids in the region adjacent to the N-terminal region were involved in releasing microfibrils and in binding to dyed cotton fabrics, indicating that the binding of the amino acids in this region might be important in the release of microfibrils from dyed cotton fabrics. 相似文献
14.
Tamura M Milenic DE Iwahashi M Padlan E Schlom J Kashmiri SV 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(3):1432-1441
Clinical utility of murine mAbs is limited because many elicit Abs to murine Ig constant and variable regions in patients. An Ab humanized by the current procedure of grafting all the complementarity determining regions (CDRs) of a murine Ab onto the human Ab frameworks is likely to be less immunogenic, except that its murine CDRs could still evoke an anti-variable region response. Previous studies with anticarcinoma mAb CC49 showed that light chain LCDR1 and LCDR2 of humanized CC49 could be replaced with the corresponding CDRs of a human Ab with minimal loss of Ag-binding activity. The studies reported in this paper were undertaken to dissect the CC49 Ag-binding site to identify 1) specificity determining residues (SDRs), the residues of the hypervariable region that are most critical in Ag-Ab interaction, and 2) those residues that contribute to the idiotopes that are potential targets of patients' immune responses. A panel of variants generated by genetic manipulation of the murine CC49 hypervariable regions were evaluated for their relative Ag-binding affinity and reactivity to sera from several patients who had been immunized with murine CC49. One variant, designated HuCC49V10, retained only the SDRs of CC49 and does not react with the anti-variable region Abs of the sera from the murine CC49-treated patients. These studies thus demonstrate that the genetic manipulation of Ab variable regions can be accomplished by grafting only the SDRs of a xenogeneic Ab onto human Ab frameworks. This approach may reduce the immunogenicity of Abs to a minimum. 相似文献
15.
Exact identification of complementarity determining regions (CDRs) is crucial for understanding and manipulating antigenic interactions. One way to do this is by marking residues on the antibody that interact with B cell epitopes on the antigen. This, of course, requires identification of B cell epitopes, which could be done by marking residues on the antigen that bind to CDRs, thus requiring identification of CDRs. To circumvent this vicious circle, existing tools for identifying CDRs are based on sequence analysis or general biophysical principles. Often, these tools, which are based on partial data, fail to agree on the boundaries of the CDRs. Herein we present an automated procedure for identifying CDRs and B cell epitopes using consensus structural regions that interact with the antigens in all known antibody-protein complexes. Consequently, we provide the first comprehensive analysis of all CDR-epitope complexes of known three-dimensional structure. The CDRs we identify only partially overlap with the regions suggested by existing methods. We found that the general physicochemical properties of both CDRs and B cell epitopes are rather peculiar. In particular, only four amino acids account for most of the sequence of CDRs, and several types of amino acids almost never appear in them. The secondary structure content and the conservation of B cell epitopes are found to be different than previously thought. These characteristics of CDRs and epitopes may be instrumental in choosing which residues to mutate in experimental search for epitopes. They may also assist in computational design of antibodies and in predicting B cell epitopes. 相似文献
16.
G. Frankel † S. M. C. Newton G. K. Schoolnik B. A. D. Stocker 《Molecular microbiology》1989,3(10):1379-1383
The H1 (now renamed fliC; lino et al., 1988) alleles specifying antigenically different Salmonella flagellins are identical at their ends but differ greatly towards the middle, where there are two hypervariable segments (regions IV and VI). The flagellar antigen, d, of Salmonella typhi, is found also as phase-1 antigen in many other Salmonella species. We cloned the H1-d gene of a strain of S. typhi and determined the nucleotide sequence of its two hypervariable regions. Comparison with gene H1-d of Salmonella muenchen showed substantial differences in region VI: four scattered amino acid differences and ten adjacent amino acids in the inferred S. typhi sequence, all of which differ from the corresponding nine amino acids in the S. muenchen sequence. The results of polymerase chain reaction amplification indicated the presence of the S. typhi version in all of 18 additional S. typhi strains and the presence of the S. muenchen version in all four non-S. typhi species with flagellar antigen d. The difference in amino acid sequence in segment VI may be responsible for the minor serological differences between antigens d of S. typhi and antigen d of S. muenchen. 相似文献
17.
Analysis of sequence diversity in hypervariable regions of the external glycoprotein of human immunodeficiency virus type 1. 总被引:45,自引:31,他引:14 下载免费PDF全文
Nucleotide sequences in three hypervariable regions of the human immunodeficiency virus type 1 (HIV-1) env gene were obtained by sequencing provirus present in peripheral blood mononuclear cells of HIV-infected individuals. Single molecules of target sequences were isolated by limiting dilution and amplified in two stages by the polymerase chain reaction, using nested primers. The product was directly sequenced to avoid errors introduced by Taq polymerase during the amplification process. There was extensive variation between sequences from the same individual as well as between sequences from different individuals. Interpatient variability was markedly less in individuals infected from a common source. A high proportion of amino acid substitutions in the hypervariable regions altered the number and positions of potential N-linked glycosylation sites. Sequences in two hypervariable regions frequently contained short (3- to 15-bp) duplications or deletions, and by amplifying peripheral blood mononuclear cell DNA containing 10(2) or 10(3) proviral molecules and analyzing the product by high-resolution electrophoresis, the total number and abundance of distinct length variants within an individual could be estimated, providing a more comprehensive analysis of the variants present than would be obtained by sequencing alone. Sequences from many individuals showed frequent amino acid substitutions at certain key positions for neutralizing-antibody and cytotoxic T-cell recognition in the immunodominant loop. The rates of synonymous and nonsynonymous nucleotide substitution in the region of this and flanking regions indicate that strong positive selection for amino acid change is operating in the generation of antigenic diversity. 相似文献
18.
Lee CV Liang WC Dennis MS Eigenbrot C Sidhu SS Fuh G 《Journal of molecular biology》2004,340(5):1073-1093
Phage-displayed synthetic antibody libraries were built on a single human framework by introducing synthetic diversity at solvent-exposed positions within the heavy chain complementarity-determining regions (CDRs). The design strategy of mimicking natural diversity using tailored codons had been validated previously with scFv libraries, which produced antibodies that bound to antigen, murine vascular endothelial growth factor (mVEGF), with affinities in the 100nM range. To improve library performance, we constructed monovalent and bivalent antigen-binding fragment (Fab) libraries, and explored different CDR-H3 diversities by varying the amino acid composition and CDR length. A Fab with sub-nanomolar affinity for mVEGF was obtained from a library with CDR-H3 diversity designed to contain all 20 naturally occurring amino acids. We then expanded the library by increasing the variability of CDR-H3 length and using tailored codons that mimicked the amino acid composition of natural CDR-H3 sequences. The library was tested against a panel of 13 protein antigens and high-affinity Fabs were obtained for most antigens. Furthermore, the heavy chain of an anti-mVEGF clone was recombined with a library of light chain CDRs, and the affinity was improved from low nanomolar to low picomolar. The results demonstrated that high-affinity human antibodies can be generated from libraries with completely synthetic CDRs displayed on a single scaffold. 相似文献
19.
The complete amino acid sequence of the variable regions of light chains derived from anti-p-azophenylarsonate antibodies from A/J mice bearing a cross-reactive idiotype is reported. At least two and probably more than three distinct light chains are associated with this idiotypically characterized antibody. The antibodies have several differences in their "framework" structures but evidence is presented indicating that all three light chain hypervariable regions have a homogeneous sequence. The data are discussed in relation to the various theories of antibody diversity. In addition, the findings support the view that hypervariable regions, idiotypic determinants, and the antibody-combining site involve, to a large extent, the same molecular structures. 相似文献
20.
Hypervariable Region of Human Immunoglobulin Heavy Chains 总被引:5,自引:0,他引:5
J. DONALD CAPRA 《Nature: New biology》1971,230(10):61-63
THE variable regions of human immunoglobulin light chains contain three areas of unusually high variability1–4. Similar hypervariable regions have been postulated for human heavy chains5, 6, but there are no amino-acid sequence data to support this idea. These hypervariable regions are particularly interesting because they may be the areas of the immunoglobulin molecule involved in antibody complementarity.We have made use of the recent observation that a variable region subclass of heavy chains is characterized by an unblocked amino-terminal residue7 and of the availability of automated sequencing techniques8, 9 to study this question in detail with additional heavy chain sequences. 相似文献