Unusual sequence numbering: Difference between revisions

The numbering of protein and nucleic acid sequences is arbitrary in structure files from the [[PDB|World Wide Protein Data Bank]] (PDB). That is, authors are free to number sequences as they wish.

'''Straightforward numbering''' assigns 1 to the amino-terminal amino acid, and counts up sequentially and monotonically to the carboxy-terminal amino acid. An example is [http://firstglance.jmol.org/fg.htm?mol=1pgb 1pgb] ([[1pgb]]). The crystallized protein is numbered 1-56, despite it being a fragment of a [http://www.uniprot.org/uniprot/P06654#sequences 448-residue full length sequence] that begins (after adding an N-terminal Met) at full-length sequence number 228.

Sometimes the residues of a protein are numbered according to a different ''reference sequence''. When there are insertions relative to the reference sequence, the additional residues may all be given the same sequence number, but marked with alphabetic insertion codes. This is frequently done in antibodies, where the reference sequence is the germline sequence, but the antibody has been somatically mutated, especially in complementarity-determining region (CDR) 3. An example is [http://firstglance.jmol.org/fg.htm?mol=1igy 1igy] ([[1igy]]). Four residues in chain B all have sequence number 82. They are distinguished by insertion codes: 82, 82A, 82B, 82C. At right is this part of the PDB file. Below are residues 81-83 showing their sequence numbers in [[FirstGlance in Jmol]]. Insertion codes are given following a caret "^". (How? See note <ref name="how1">Click ''Find'' and enter ''chain=B and 81-83. Click ''Isolate'' and check ''Atoms with Halos''. Zoom in. In the left center after "Halos around:" click ''Change'', and then ''Clear Halos''. Check ''Sequence numbers'' (near the bottom of the upper left panel).</ref>)

It is not uncommon for a surface loop of the crystallized protein to be disordered. Often such loops are [[Intrinsically Disordered Protein|intrinsically disordered]]. The disorder blurs the electron density map for that loop, and the loop residues are not given coordinates in the model: they are missing in the model. However, they were not missing in the crystallized protein. This causes a gap in the sequence numbers in the PDB file. An example is [http://firstglance.jmol.org/fg.htm?mol=2ace 2ace] ([[2ace]]). Residues 485-489 are missing in the 3D crystallographic model due to disorder in the crystal. Also missing are 3 N-terminal, and 2 C-terminal residues.  FirstGlance in Jmol tabulates missing residues, and marks regions of the 3D model where residues are missing with "empty baskets".

Rarely, sequence numbers do not increase monotonically from N to C terminus. An example<ref>Thanks to Rachel Kramer Green of [[RCSB]] for this example.</ref> is [http://firstglance.jmol.org/fg.htm?mol=4zwj 4zwj] ([[4zwj]]). In this chimeric protein, chain A is numbered 1002-1161 continuing 1-326 continuing 2012-2361. That is, there are sudden jumps in numbering of consecutive amino acids: 1161 to 1, and 326 to 2012. At right is an excerpt from the ATOM records of the [[PDB file]] for 4zwj chain A.

== References ==