PDBsum entry 1g9e

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protein links
Immune system PDB id
Protein chain
117 a.a. *
* Residue conservation analysis
PDB id:
Name: Immune system
Title: Solution structure and relaxation measurements of an antigen-free heavy chain variable domain (vhh) from llama
Structure: H14. Chain: a. Engineered: yes
Source: Lama glama. Llama. Organism_taxid: 9844. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932
NMR struc: 20 models
Authors: J.-G.Renisio,J.Perez,M.Czisch,M.Guenneugues,O.Bornet, L.Frenken,C.Cambillau,H.Darbon
Key ref:
J.G.Renisio et al. (2002). Solution structure and backbone dynamics of an antigen-free heavy chain variable domain (VHH) from Llama. Proteins, 47, 546-555. PubMed id: 12001233 DOI: 10.1002/prot.10096.abs
23-Nov-00     Release date:   23-Oct-02    
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Protein chain
No UniProt id for this chain
Struc: 117 a.a.
Key:    Secondary structure  CATH domain


DOI no: 10.1002/prot.10096.abs Proteins 47:546-555 (2002)
PubMed id: 12001233  
Solution structure and backbone dynamics of an antigen-free heavy chain variable domain (VHH) from Llama.
J.G.Renisio, J.Pérez, M.Czisch, M.Guenneugues, O.Bornet, L.Frenken, C.Cambillau, H.Darbon.
Camelids, (dromedaries, camels, and llamas) produce heavy-chains antibodies, with their antigen recognition sites composed of a single VH-like domain, referred to as VHH. The solution structure of one of these VHHs domains (VHH-H14), raised against the alpha subunit of the human chorionic gonadotropin hormone (hCG), has been determined by (15)N heteronuclear three-dimensional NMR spectroscopy. The framework is well resolved within the set of 20 best-calculated NMR structures and is close to that of classical VH domains from vertebrate antibodies, consisting of two antiparallel beta-sheets organized in a beta-barrel. Loops display a lower precision, especially the Complementarity Determining Regions (CDRs), involved in antigen recognition. Comparison of the three-dimensional VHH-H14 solution structure with its previously solved crystal structure (Spinelli et al., Nature Struct. Biol. 1996;3:752-757) reveals a high similarity to the framework, whereas significant conformational differences occur on CDRs, leading to the assumption that the antigen recognition site is a more mobile part. In order to deepen our insights into the dynamics of VHH-H14 in solution, (15)N relaxation was measured with longitudinal R1 and transverse R2 self-relaxation rates, and (15)N steady-state heteronuclear nuclear Overhauser enhancements (NOE), making it possible to probe picosecond-to-millisecond internal motions. Determination of dynamic parameters (S(2), tau(e), and Rex) through the Lipari-Szabo Model-free approach enables the identification of several regions with enhanced dynamics. Especially, the mobility measurements from NMR confirm that the antigen recognition site is the most mobile part of the VHH-H14 domain on picosecond-to-nanosecond fast time scales. Several residues belonging to the three CDRs are submitted to chemical exchange processes occurring on slow microsecond-to-millisecond time scales, suggesting that the formation of the VHH/antigen complex should be accompanied by structural changes.
  Selected figure(s)  
Figure 4.
Figure 4. Left: Superimposition of VHH-H14 NMR average (yellow) and crystal structures (red). Middle: Superimposition of CDR3 from the 20 best calculated structures. Right: Superimposition of the loop from the NMR average (light blue) and crystal structures (dark blue).
Figure 5.
Figure 5. A: TURBO-FRODO representation of the averaged NMR backbone conformation with the residues showing significant chemical exchange contribution to their R2 relaxation rates colored in red. B: GRASP representation of the molecular surface of H14 in a similar orientation. The residues belonging that define a crevice at the top of the three CDRs are labeled.
  The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2002, 47, 546-555) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20141756 M.Lignell, and H.C.Becker (2010).
Recognition and binding of a helix-loop-helix peptide to carbonic anhydrase occurs via partly folded intermediate structures.
  Biophys J, 98, 425-433.  
  19241371 K.Conrath, A.S.Pereira, C.E.Martins, C.G.Timóteo, P.Tavares, S.Spinelli, J.Kinne, C.Flaudrops, C.Cambillau, S.Muyldermans, I.Moura, J.J.Moura, M.Tegoni, and A.Desmyter (2009).
Camelid nanobodies raised against an integral membrane enzyme, nitric oxide reductase.
  Protein Sci, 18, 619-628.  
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