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
