Looking for ONE SET of a BCR's full gDNA, mRNA, amino acid and structure Data

Hi all,
I’m new to BCR/Antibody repertoire area. I realized the following data will help me a lot to do a presentation to show the reason behind primer design for scFv library construction from B cells. But I cannot find one whole set of them.

One human BCR(or antibody, can be IgG, IgM or IgE)'s:

  1. (Optional) full gDNA sequence (after VDJ recombination, with annotation: Heavy chain [ VDJ and C ] and Light chain [ VJ and C ])
  2. Full mRNA sequence (with annotation)
  3. Amino acid (with annotation, or it could be deduced)
  4. Structure (Like those in PDB, which I can view in software like PyMOL)

I spent a whole day to look for one set but failed. What I have got are:

  1. Two IgG precursor sequences with one puzzling link to light chain’s structure [One set]
    anti-RhD monoclonal T125 precursor
    Heavy chain
    Light chain
    Notes: With one structure link in the light chain. But I do not understand the connections between “anti-RhD monoclonal T125” in the sequence title and “Kir3dl1*015” in the sturcture title.
    Also they do not have detailed V(D)J_C annotations for sequence.
  2. IgM full mRNA seq with no structure info [Two sets]
    a. Homo sapiens 2G9 monoclonal IgM
    Heavy chain
    Light chain
    b. Homo sapiens 9F11 monoclonal IgM
    Heavy chain
    Light chain
    Notes: The sequences look good. But I do not know how to search the structure data in database like PDB. Specifically, I do not know which keywords I should use and where to search. When I put “2G9” in the PDB search box, the results are “4MZN”, “4DUC”, and “4DUF”. Again, I lost. What’s the relationship between them?
  3. IgG sturcture data with no sequence data [One set]:
    1HZH on PDB
    Notes: This is the only one, intact human antibody structure, mentioned in PDB Education Portal for Antibody under section “Exploring the Structure”.
    (Two small question here: in the .pdb 3D file, 233rd and 234th amino acids are linked together in the sequence of Chain “/K/1”, but are not linked together in the cartoon structure. Is this normal? The sequence lengths are not the same in fasta and the model in the .pdb file. E.g., 457aa for Heavy Chain in fasta, but 487aa for it in structure model. Why is that?)
    When I searched the keyword “1HZH” in NCBI Nucleotide, The results are also confusing. I wanted to find the annotated sequence for 1HZH (I guess it should be somewhere online).

Also, I noticed that it is easier to find Fab’s structure than the intact antibody. One whole set of a Fab would also be of great help.

Thanks in advance!

1 Like

I would take a look at this paper to start:

Liao, H.-X. et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 496, 469–76 (2013).

See the Author Information section at the end for PDB and GenBank accession numbers.

Thanks Jason!!
Seems it is what I’m looking for! I have downloaded the .PDB file. It is a Fab’s structure. But the sequences mentioned in the “Author Information section” contain only V(D)J, no sequences for CH1 and CL.
I will go through the sequences and probably the paper to find some details. Will update here later.

Thanks again!


Based on the paper mentioned by @javh, and the related papers (antibodies neutralizing HIV) suggested by PubMed, I have tried to search for a whole set but failed again. Here is the summary.

With structure for Fab, sequence for variable region(VDJ), but no constant region(CH1 and CL):

  1. Liao, Hua-Xin, et al. “Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus.” Nature 496.7446 (2013): 469-476.

  2. Scheid, Johannes F., et al. “Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding.” Science 333.6049 (2011): 1633-1637.

  3. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01.

  4. Wu, Xueling, et al. “Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing.” Science 333.6049 (2011): 1593-1602.

  5. Doria-Rose, Nicole A., et al. “Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies.” Nature 509.7498 (2014): 55-62.

  6. Diskin, Ron, et al. “Increasing the potency and breadth of an HIV antibody by using structure-based rational design.” Science 334.6060 (2011): 1289-1293.

  7. Prabakaran, Ponraj, et al. “Structural mimicry of CD4 by a cross-reactive HIV-1 neutralizing antibody with CDR-H2 and H3 containing unique motifs.” Journal of molecular biology 357.1 (2006): 82-99.

If you only need the constant region sequences, you can probably just use the artificially spliced exon sequences from the IMGT reference database.