Representing Quaternary Structure

Tom Goddard
November 17, 2008

How are multimeric assemblies described in PDB entries?
- New mmCIF specification published August 2008.
How can Chimera better depict assemblies?
- Automatically recognized and color identical and homologous chains.
- Name chains using biological names plus chain id VP8 (R).
What is needed handle symmetric an non-symmetric molecule placement?
- Capability to apply standard symmetry groups to PDB monomers.
- Ability to save multimeric assemblies created in Chimera.
- Identify all unique interfaces in symmetric complexes.
- File format for placing multiple copies of PDB entries in EM maps.

Quaternary Structure in PDB Entries

Representation of viruses in the remediated PDB archive.
Lawson CL, Dutta S, Westbrook JD, Henrick K, Berman HM.
Acta Crystallogr D Biol Crystallogr. 2008 Aug;D64(Pt 8):874-82. Epub 2008 Jul 17.

Remediated RCSB symmetry specification

Paramecium bursaria chorella virus type 1 (PBCV-1) is PDB entry 1m4x.
Has 3 chains A,B,C forming a trimer.
1680 trimers for the capsid.

mmCIF Example: 1m4x.cif describes seven subassemblies

#
loop_
_pdbx_struct_assembly.id 
_pdbx_struct_assembly.details 
1   'complete icosahedral assembly'                
2   'icosahedral asymmetric unit'                  
3   'icosahedral pentamer'                         
4   'icosahedral 23 hexamer'                       
5   'pentasymmetron capsid unit'                   
6   'trisymmetron capsid unit'                     
PAU 'icosahedral asymmetric unit, std point frame' 

#
loop_
_pdbx_struct_assembly_gen.assembly_id 
_pdbx_struct_assembly_gen.oper_expression 
_pdbx_struct_assembly_gen.asym_id_list 
_pdbx_struct_assembly_gen.entity_inst_id 
1   (1-60)(61-88)           A,B,C . 
2   (61-88)                 A,B,C . 
3   (1-5)(61-88)            A,B,C . 
4   (1,2,6,10,23,24)(61-88) A,B,C . 
5   (1-5)(63-68)            A,B,C . 
6   (1,10,23)(61,62,69-88)  A,B,C . 
PAU (P)(61-88)              A,B,C . 

# 
loop_
_pdbx_struct_oper_list.id 
_pdbx_struct_oper_list.type 
_pdbx_struct_oper_list.matrix[1][1] 
_pdbx_struct_oper_list.matrix[1][2] 
_pdbx_struct_oper_list.matrix[1][3] 
_pdbx_struct_oper_list.vector[1] 
_pdbx_struct_oper_list.matrix[2][1] 
_pdbx_struct_oper_list.matrix[2][2] 
_pdbx_struct_oper_list.matrix[2][3] 
_pdbx_struct_oper_list.vector[2] 
_pdbx_struct_oper_list.matrix[3][1] 
_pdbx_struct_oper_list.matrix[3][2] 
_pdbx_struct_oper_list.matrix[3][3] 
_pdbx_struct_oper_list.vector[3] 
P  'transform to point frame'    0.30901699  -0.50000000 0.80901699  0.00000  0.80901699  -0.30901699 -0.50000000 0.00000  
0.50000000  0.80901699  0.30901699  -0.00000 
1  'point symmetry operation'    1.00000000  0.00000000  0.00000000  0.00000  0.00000000  1.00000000  0.00000000  0.00000  
0.00000000  0.00000000  1.00000000  0.00000  
2  'point symmetry operation'    0.80901699  0.30901699  0.50000000  0.00000  0.30901699  0.50000000  -0.80901699 0.00000  
-0.50000000 0.80901699  0.30901699  0.00000  

...

60 'point symmetry operation'    -0.50000000 -0.80901699 -0.30901699 0.00000  0.80901699  -0.30901699 -0.50000000 0.00000  
0.30901699  -0.50000000 0.80901699  0.00000  
61 'build point asymmetric unit' 1.00000     0.00000     0.00000     0.0      0.00000     1.00000     0.00000     0.0      0.00000 
0.00000     1.00000     0.0      
62 'build point asymmetric unit' 0.999773    0.014247    -0.015805   -49.486  -0.014842   0.999161    -0.038166   14.993   
0.015248    0.038393    0.999147    32.902   

...

88 'build point asymmetric unit' 0.967112    0.161474    -0.196522   -130.071 -0.188316   0.973929    -0.126494   95.792   
0.170973    0.159342    0.972305    -1.525   


# 
loop_
_pdbx_struct_legacy_oper_list.id 
_pdbx_struct_legacy_oper_list.name 
_pdbx_struct_legacy_oper_list.matrix[1][1] 
_pdbx_struct_legacy_oper_list.matrix[1][2] 
_pdbx_struct_legacy_oper_list.matrix[1][3] 
_pdbx_struct_legacy_oper_list.vector[1] 
_pdbx_struct_legacy_oper_list.matrix[2][1] 
_pdbx_struct_legacy_oper_list.matrix[2][2] 
_pdbx_struct_legacy_oper_list.matrix[2][3] 
_pdbx_struct_legacy_oper_list.vector[2] 
_pdbx_struct_legacy_oper_list.matrix[3][1] 
_pdbx_struct_legacy_oper_list.matrix[3][2] 
_pdbx_struct_legacy_oper_list.matrix[3][3] 
_pdbx_struct_legacy_oper_list.vector[3] 
1    1x61  1.00000000  0.00000000  0.00000000  0.00000    0.00000000  1.00000000  0.00000000  0.00000    0.00000000  0.00000000  
1.00000000  0.00000    
2    1x62  0.99977300  0.01424700  -0.01580500 -49.48600  -0.01484200 0.99916100  -0.03816600 14.99300   0.01524800  0.03839300  
0.99914700  32.90200   

...

1679 60x87 -0.28149639 -0.95353767 0.10734706  -20.06292  0.76749273  -0.29088592 -0.57126126 -188.26516 0.57594612  -0.07842024 
0.81371768  -71.92725  
1680 60x88 -0.38403872 -0.91790149 -0.09986197 -11.99060  0.75511638  -0.24999640 -0.60605334 -134.06850 0.53133210  -0.30815591 
0.78912963  -89.32390

PDB Example: 1m4x.pdb lists 1680 matrices

REMARK 300                                                                      
REMARK 300 BIOMOLECULE: 1                                                       
REMARK 300 THIS ENTRY CONTAINS THE UNIQUE NON-CRYSTALLOGRAPHIC REPEAT           
REMARK 300 UNIT, WHICH CONSISTS OF 3  CHAIN(S). SEE REMARK 350 FOR              
REMARK 300 INFORMATION ON GENERATING THE BIOLOGICAL MOLECULE(S).                
REMARK 300 THE ASSEMBLY REPRESENTED IN THIS ENTRY HAS REGULAR                   
REMARK 300 ICOSAHEDRAL POINT SYMMETRY (SCHOENFLIES SYMBOL = I).                 
REMARK 350                                                                      
REMARK 350 GENERATING THE BIOMOLECULE                                           
REMARK 350 COORDINATES FOR A COMPLETE MULTIMER REPRESENTING THE KNOWN           
REMARK 350 BIOLOGICALLY SIGNIFICANT OLIGOMERIZATION STATE OF THE                
REMARK 350 MOLECULE CAN BE GENERATED BY APPLYING BIOMT TRANSFORMATIONS          
REMARK 350 GIVEN BELOW.  BOTH NON-CRYSTALLOGRAPHIC AND                          
REMARK 350 CRYSTALLOGRAPHIC OPERATIONS ARE GIVEN.                               
REMARK 350                                                                      
REMARK 350 BIOMOLECULE: 1                                                       
REMARK 350 APPLY THE FOLLOWING TO CHAINS: A, B, C                               
REMARK 350   BIOMT1   1  1.000000  0.000000  0.000000        0.00000            
REMARK 350   BIOMT2   1  0.000000  1.000000  0.000000        0.00000            
REMARK 350   BIOMT3   1  0.000000  0.000000  1.000000        0.00000            
REMARK 350   BIOMT1   2  0.999773  0.014247 -0.015805      -49.48600            
REMARK 350   BIOMT2   2 -0.014842  0.999161 -0.038166       14.99300            
REMARK 350   BIOMT3   2  0.015248  0.038393  0.999147       32.90200            
...
REMARK 350   BIOMT1  1680 -0.384039 -0.917901 -0.099862      -11.99060          
REMARK 350   BIOMT2  1680  0.755116 -0.249996 -0.606053     -134.06850          
REMARK 350   BIOMT3  1680  0.531332 -0.308156  0.789130      -89.32390

3D Complex: A Structural Classification of Protein Complexes

3D complex: a structural classification of protein complexes.
Levy ED, Pereira-Leal JB, Chothia C, Teichmann SA.
PLoS Comput Biol. 2006 Nov 17;2(11):e155. Epub 2006 Oct 5.

More than half of RCSB structures are homo- or heteromeric protein complexes.

Chimera does not recognize and identify identical or similar chains in multi-chain complexes.

Listing all unique contact interfaces between chains would be useful.

Protein Quaternary Structures Server (EBI)

Breakdown of generated oligomers by type:

As of Nov 12 2008 there are 52444 entries loaded with the following exceptions:

nucleic acid and nuclei acid/protein complexes excluded all virus coat assemblies related entries excluded.

1bbs 1cde 1cyc 1hrb 1lbt 1xys 2cha 2lgs 1bcf
1gto 1xim 2xim 3pcn 3pca 3pcf 3pch 3pci 3pcj
3pck 3pcl 3pcm 3xim 1bcf 2lgs 123d 1ruo 1wio
1wip 3tra

The above entries are available via the PDBidcode search mechanism.

---------------------------------------------------------
 Oligomer         Number      Number       Number       Examples
  size            generated   homo-        hetero-
                   (accepted)   (accepted)    (accepted)
---------------------------------------------------------
 monomer/complex   19491
 dimer             17903 (16472)  13705 (12363)   4194  (4109)
 trimer             3554  (3496)   1664  (1611)   1890  (1885)
 tetramer           6013  (5962)   3823  (3785)   2190  (2177)
 pentamer            398   (394)    195   (195)    203   (199)   1BOV  (homo) 1A2K  (het)
 hexamer            1862  (1845)   1158  (1143)    704   (702)   1AEI  (homo) 1AFV  (het)
 heptamer            100    (99)     48    (48)     52    (51)   7AHL  (homo) 1LTI  (het)
 octamer             786   (779)    453   (450)    333   (329)   1AHU  (homo) 1BFV  (het)
 nonamer              88    (88)     11    (11)     77    (77)   1FWA
 decamer             157   (157)     91    (91)     66    (66)   1GTP
 undecamer            17    (17)     14    (14)      3     (3)   1WAP
 dodecamer           472   (472)    215   (215)    257   (257)   1COA  (homo) 1IZB  (het)
 tetradecamer         46    (46)     34    (34)     12    (12)   1GRL  (homo) 1AVO  (het)
 hexadecamer          98    (98)     16    (16)     82    (82)   2HLC  (homo) 1AA1  (het)
 octadecamer          27    (26)      6     (6)     21    (20)   1KZU
 21meric              41    (41)      0     (0)     41    (41)   1AON  (homo)
 24meric             144   (140)     85    (85)     59    (55)   1AEW  (homo) 3PCA  (het)
 26meric              14    (14)      0     (0)     14    (14)   1OCC
 28meric              21    (21)      1     (1)     20    (20)   1PMA
---------------------------------------------------------

Non-symmetric placement of molecules in electron microscopy

Desmosomes from a structural perspective.
Stokes DL.
Curr Opin Cell Biol. 2007 Oct;19(5):565-71. Epub 2007 Oct 22. Review.

HIV Spike EM Tomography

June 2006 EM tomography example fitting HIV gp120/gp41 spikes using Chimera. Spikes recognize target cells and initiate viral fusion. Illustrates combined use of tomography and structure averaging approach.

Zhu P, Liu J, Bess J Jr, Chertova E, Lifson JD, Grise H, Ofek GA, Taylor KA, Roux KH.
Distribution and three-dimensional structure of AIDS virus envelope spikes.
Nature. 2006 Jun 15;441(7095):847-52. Epub 2006 May 24.

Ribosome positions in Spiroplasma melliferum

Mapping 70S ribosomes in intact cells by cryoelectron tomography and pattern recognition.
Ortiz JO, Förster F, Kürner J, Linaroudis AA, Baumeister W.
J Struct Biol. 2006 Nov;156(2):334-41. Epub 2006 Jun 3