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Dear colleagues, Thanks to all who replied to my question. Among the most helpful answers was the one from Ralf W. Grosse-Kunstleve who carried out Protein Data Bank searches (see below). Best regards, Lionel Original posting I would be very interested and much grateful having references (bibliographic data, PDB entry code, web link...) on 3D structures of covalently linked (engineered or not) protein-protein complexes (e.g. heterodimers). Our own survey of the literature was not very "successful". Here is a summary of the responses: Marko Hyvönen [EMAIL PROTECTED] not sure what you mean exactly with your question, but I have few suggestions which could be of use. All members of the TGFbeta superfamily are covalent dimers (see 2arp, 2tgi, 2bmp etc) with a disulfide in between. Rad51-BRC4 repeat structure by Luca Pellegrini has a BRC4 peptide bound to Rad51, and construct crystallised had the peptide covalently fused to the N-terminus rad51. PDB: 1n0w. Roberto Steiner [EMAIL PROTECTED] One example: In the Neuron (2004) 41:573-86 Zhou et al. describe the structure of a KChIP1/Kv4.2 chimeric complex (PDB code 1S6C). Recently, Pioletti etl al (2006) Nat. Struct. Mol. Biol., 13:987-995 have solved the structure of the "natural" complex showing (PDB code 2I2R) that the structure of the chimera is non-physiological. Boaz Shaanan [EMAIL PROTECTED] Does an Fv fragment fall into your definition of covalently linked complex (between Vl and Vh domains) ? If so, you'll probably find a few in the pdb. Brad C Bennett [EMAIL PROTECTED] Definitely an engineered example for you: This is a paper describing (among other things) the 3D structure of a ligand-induced homodimer of E. coli DHFR (a functional monomer), via covalent linkage of the ligands themselves. Designing Protein Dimerizers: The Importance of Ligand Conformational Equilibria Jonathan C. T. Carlson, Aaron Kanter,Guruvasuthevan R. Thuduppathy,Vivian Cody, Pamela E. Pineda,R. Scott McIvor,and Carston R. Wagner J. Am. Chem. Soc., 125 (6), 1501 -1507, 2003 Menachem Shoham [EMAIL PROTECTED] Here is one reference from the lab of Cynthia Wolberger at Johns Hopkins. Eddins, MJ. A1 - Carlile, CM. A1 - Gomez, KM. A1 - Pickart, CM. A1 - Wolberger, C. JF - Nature Structural & Molecular Biology VL - 13 IS - 10 SP - 915 Y1 - 2006 T1 - Mms2-Ubc13 covalently bound to ubiquitin reveals the structural basis of linkage-specific polyubiquitin chain formation. A number of years she had also solved a structure of the maltose-binding-protein fused to a DNA-binding protein. Philippe Dumas [EMAIL PROTECTED] To my knowledge the most amazing example of such covalently linked proteins is from a virus structure solved in Jack Johnson's group. This virus has a protein shell with a (shell thickness)-to-(virion radius) ratio close to that of a football and everything holds together because the protomers are litterally sewed by covalent links. Valerie Hindie [EMAIL PROTECTED] from this database you can find all complexes pdb-id: http://www.mrc-lmb.cam.ac.uk/genomes/elevy/3dcomplex/Home.cgi Janet Deane [EMAIL PROTECTED] We successfully solved the structure of a protein with it's binding partner (although this was a fraction of the full protein that turned out to be peptide-like). PDB code: 1RUT Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex. Deane JE, Ryan DP, Sunde M, Maher MJ, Guss JM, Visvader JE, Matthews JM. EMBO J. 2004 Sep 15; 23(18): 3589-3598. Paper describing the engineering was: Design, production and characterization of FLIN2 and FLIN4: the engineering of intramolecular ldb1:LMO complexes. Protein Eng. 2001 Jul;14(7):493-9. Ralf W. Grosse-Kunstleve [EMAIL PROTECTED] I found this question interesting, therefore I quickly searched the entire PDB V3 (http://wwpdb-remediation.rutgers.edu/) for LINK records linking two standard amino acid residues, excluding chain links and same-chain disulfides. Here are the results: http://cci.lbl.gov/~rwgk/tmp/protein_protein_links/2007_02_26_1220/file_names_protein_protein_links http://cci.lbl.gov/~rwgk/tmp/protein_protein_links/2007_02_26_1220/protein_protein_links In the second file, look for "protein_protein_links" to find the LINK records. At first sight there are only a few false positives (residue linked to itself), which I didn't filter out because I want to tell the wwPDB about it. Let me know if you find more false positives. See also http://cci.lbl.gov/~rwgk/tmp/protein_protein_links/2007_03_05_1256/file_names_intra_chain_ssbonds http://cci.lbl.gov/~rwgk/tmp/protein_protein_links/2007_03_05_1256/intra_chain_ssbonds for SSBOND records excluding intrachain disulfides. Lionel Mourey e-mail: lionel dot mourey at ipbs dot fr Groupe de Biophysique Structurale Département "Mécanismes Moléculaires des Infections Mycobactériennes" IPBS-CNRS UMR 5089 / 205 route de Narbonne 31077 / TOULOUSE Cedex FRANCE Tel : +33 (0)561 175 436 Fax : +33 (0)561 175 994 |
