Immunoglobulin Structure and Function in a nutshell

The two principal structures of immunoglobulins are now available in the Gallery. The trans form is the stable form in the absence of antigen, while the cis form is stable in the presence of antigen and complement. The two forms are quaternary isomers, differing almost only in the arrangement of subunits. It is now possible to give names to the various domains that suggest their shapes and functions. The word "elbow" is already used to describe the short flexible linking sequences between domains and the word "bridge" is already used to describe the longer flexible sequence in the middle of the heavy chain. These names can be retained. The light chain has two domains separated by an elbow of residues 104-109. Residues 1-103, previously named N_L, can now be named "antigen jaw_L", while residues 110-214, previously named C_L can be named "left-hand_L". The heavy chain domains can be similarly renamed (old names in parentheses): 1-111 "antigen jaw_H" (N_H); 114-230 "left-hand_H" (C_H1); 232-243 "bridge" or now possibly "latch"; 244-357 "right-hand" (C_H2); and 365-478 "complement jaw" (C_H3). Elbows are 112-113 and 358-364. The orientational relationship between a jaw and a left-hand is similar to that seen in the L chain of IgG2 (1YEF.pdb). Left hands clasp each other to form the antigen-binding complex, with the Complementarity Determining Regions on the inner surfaces of the jaws. Right-hands clasp right-hands to form the complement-binding complex. The switch between isomers involves four disulfide bridges exchanging partners, first the disulfides linking “left-hands” and then the disulfides in the “bridge”. This last exchange of disulfide partners may serve to lock the complement-binding domains into their binding conformation – hence the “bridge” may be better described as a “latch”. More work required!

Conventions for naming files

The structure files of native proteins draw most of their information from Protein Data Bank files and are expressed in the same format. Therefore it is appropriate to name the native protein files by adding short prefixes or suffixes to the names of the original crystal structures supplied by the Protein Data Bank. I have chosen to use the prefix "n" to indicate a native structure, together with a numeral. "n1_" indicates a first approximation to the native structure using subunit rearrangement only. "n2_" indicates a second approximation achieved by restoring the conformation of a small number of residues, usually less than 10% of the total sequence. "n3_" would be used for a full relaxation of the crystal structure into a native structure using a force field. For α₂β₂ heterotetramers, e.g. hemoglobin, there are 3 possible quaternary isomers and I have chosen to use suffixes to indicate which isomer the file describes. Where there are existing abbreviations for the isomers it is best to retain them. For hemoglobin, I use the suffix "_r" for the R state, "_t" for the principal T state and "_t2" for the alternate T state that might be significant in the absence of polyanions. In the case of elongated proteins in α₂β₂ heterotetramers, such as the heavy chain of immunoglobulin, one isomer can be described as "cis" and the other two as "trans". A pair of immunogobulin structures will be placed in the Gallery shortly, the cis form with the suffix "_cis" and the principal trans form with the suffix "_tr".

Improved site for Structure Gallery

The Gallery of 3D Structures has now been made a free-standing site with all its software on the Nativeproteins server. This has fixed some failings in the control buttons and check-boxes of the Jmol interface. This new version of Jmol has been chosen so that it is prevented from writing to your computer - it will not be seen by your browser as a potential threat, but, on the other hand, it cannot write a jpg file to save an image. For those who prefer to use their own structure viewer, the files of atomic coordinates are also provided for download. I have established some conventions for constructing and naming the files of reassembled atomic coordinates. These will be detailed in a future post.

Gallery restored with updated Jmol

The Gallery of 3D Native Protein Structures has now been restored. The files use the updated version of Jmol supplied by the RCSB Protein Data Bank. Please advise me if any functionality is missing by email to dvanselow@hotmail.com

Gallery temporarily out-of-order

Apologies for the temporary loss of function in the Gallery of 3D Native Protein Structures linked to this blog. The Gallery depends on the software used by the RCSB Protein Data Bank. As they have updated their software, the html files in the Gallery now need to be updated.

A naturally occurring cross-linked TIM validates these Native Structures

Triose phosphate isomerase (TIM) from the hyperthermophilic bacterium Thermotoga maritima crystallizes as a tetramer that appears to be a pair of dimers similar to those observed in crystals of other TIMs (Maes et al. 1999). The two dimers are joined by disulphide bonds between pairs of Cys142. As noticed by Gayathri et al.(2007) this linkage is not consistent with the dimer seen in crystals being the same as the dimer in solution and Gayathri et al. conclude that the "tetramerization appears to be a crystallization artifact."
However, when the TIM monomers are docked by the methods described in this blog, the pairs of Cys142 are naturally in close proximity. The native structure of TIM from T. maritima is now included in the Gallery. It can be seen that the disulfide bond is indeed a natural part of the quaternary structure and the form of dimer seen in crystals is the actual artifact.

Mirror site for scientists in China

It has come to my notice that our colleagues in China cannot access this blog but can access the Structure Gallery. Therefore I will maintain a copy of this blog and the companion Enzyme Function blog on the server used by the Gallery. Please direct any colleagues who cannot access Blogspot to
www.nativeproteins.com/blog/