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3DSwap - Help Index | Curated Knowledgebase of 3D Domain Swapping in Proteins: Help Page

3D Domain Swapping : Introduction:

3D domain swapping is a mechanism by which two or more protein molecules form a dimer or higher oligomer by exchanging an identical structural element. In domain swapping, native intramolecular interactions are replaced by their intermolecular counterparts. It is one of the most interesting structural features that have been observed in an array of crystal structures. This process emerges as a ubiquitous mechanism for homo-oligomer formation in many completely unrelated protein systems. Domain swapping is an interesting phenomenon due to the swapping feature of these structure irrespective of the absence of significant sequence or structure similarity; they are important due to a variety of functions mediated by this macromolecules in swapped conformation.


3DSwap - Curated Knowledgebase of 3D domain swapping:

3DSwap is a comprehensive collection of protein structures that are reported to be involved in 3-Dimensional Domain Swapping. 3DSwap provides literature curated information about 3D Domain Swapping in Proteins. 3D domain swapping is a mechanism for two or more protein molecules to form a dimer or higher oligomer by exchanging an identical structural element (“domain”). It has been first reported in Diphtheria Toxin [PDB ID:1DDT]. 3DSwap provides detailed information various information about swapping, protein-protein interface, extent of swapping etc. Information related to domain swapping were extracted from orginal research publications after extensive literature curation.


3D Domain Swapping : Structural features:

3D Domain Swapping : The structural phenomenon observed in a wide array of structures, where two or more chains form an oligomeric conformation by mutually sharing a structural segment between the chains.


Hinge Region : The residues(or short sequence) which connects the secondary minor and major region is called as hinge region. The hinge region can be a loop, sheet, helix or few residues.

Swapped region : A globular domain (or sometimes one or few elements of secondary structure) that is intertwined with an identical protein chain, is referred as the swapped segment. The swapped domain retains an environment essentially identical to that of the same domain in a protein monomer.

Secondary Minor Region : The entire domain or a part of one chain which is swapped with the other domain of the neighbouring chain is referred as "secondary minor region" or Guest. Secondary minor region is an alternate definition used to define hinge region to explain the secondary regions with more clarity.

Secondary Major Region * : The region which interacts with the secondary minor region is termed as Secondary major region or Host.

Quasi-Domain Swapping : Quasidomain swapping refers to the structures where some proteins form domain swapped oligomers without a known closed monomer. If these proteins have homologues known to be closed monomers, these oligomers are considered to be .quasidomain swapped. Examples of quasidomain swapping include crystallin, pheromone/odorant binding/transport proteins, RYMV (viral capsid protein) , human cystatin C (protease inhibitor) etc.

Bonafide Domain Swapping : Bonafide domain swapping refers to structures where both the monomer and the dimer of a molecule exist in stable forms, where the dimer adopts a domain-swapped conformation and the monomer adopts a closed conformation. Examples of Bonafide domain swapping includes diphtheria toxin, RNases, CD2 (T-cell adhesion), Spo0A (development regulation) etc.

Extent of swapping * : Extent of swapping is a new method developed to assess of the extent of swapping with respect to the protein chains involved in swapping. For example, for a protein with 2 chains X, Y, the extent of swapping is calculated using the formula given below:

Where RMI= Number of residues in secondary major interface, Rmi = Number of residues in secondary minor interface. RChain:1 = Number of residues in Chain 1 and RChain:2 = Number of residues in Chain 2. Based on the percentage of extent of swapping observed in different structures, we have classified the structures in to three major classes as ‘Extensive swapping’, ‘Moderate swapping’ and ‘Minimum swapping’. Extensive swapping refers to the oligomeric structures where the ‘Extent of Swapping’ is observed within the range of 35%-100% [Example: 1A64]. Moderate swapping refers to the oligomeric structures where the ‘Extent of Swapping’ is observed within the range of 15%-35% [Example: 1OQF]. Minimum swapping refers to the oligomeric structures where the ‘Extent of Swapping’ is observed within the range of 1-15% [Example: 1K6W].

* NB. New concept introduced in 3Dswap Knowledgebase.

3DSwap - Browse:
3DSwap can be browsed using two interfaces:

3DSwap - Browse:

Users can search the 3DSwap database based on various keywords: "Keyword Search" can be performed using PDB ID, PDB-HEADER data, PDB-GO, Pfam domains and SCOP annotations based keywords.


3DSwap - Literature based Protein Structural Curation Method:

Protein structures presented in 3DSwap was curated using a new curation approach. We combined literature mining approach and manual structural analysis and visualization in an iterative fashion to identify hinge and swapped region features of 3D domain swapping to structures. We defined this approach as “literature based protein structural curation”. PDB ID, Chain ID, Oligomeric state, Hinge Regions, Swapped Region, Extent of Swapping, Sequence Data and Reference fields were curated and stored in the database.


3DSwap - Visualization:

Interactive visualization options are provided to visualize and analyse various aspects of protein structures involved in 3D domain swapping using Jmol and Rasmol. Jmol is a Java based web-applet that enables the users to visually analyze the molecular structures within a web browser. Jmol applet loaded with 11BG can be obtained from the ‘Jmol logo’. Rasmol is a standalone molecular visualization application, which can be installed on different operating systems. We provide Rasmol scripts for the interactive analysis of the structures in local machine. Rasmol script can be obtained by clicking the 'Rasmol logo'.


3DSwap - Sequence Features

Sequence analysis section of 3DSwap provides two features:


3DSwap - Structure Features:

Hydrogen bonds, solvent accessibility, secondary structure, JOY-based representation were obtained using JOY package for all the entries in the database. Hydrogen bonds were calculated using hbond routine, solvent accessibility information is generated using psa and secondary structure files are generated using sstruc in JOY package. JOY files and tem files are also provided for every entry reported in the database.


3DSwap - Function Annotation:

Function annotation information derived from GO annotations and Pfam databases are provided to understand the functional features of the proteins enlisted in 3DSwap.


3DSwap - Keyword search:

Users can utlilize the search interface to retrieve structures that matching user keywords. Users can use individual PDB IDs without chain information (for example "1CKS" or keywords in PDB header "RNAase"). Search accepts only single query at a time. Users can also utilize search options to search 3DSwap using Superfamily level annotations from Conserved Domains Database (NCBI-CDD), Protein domain annotations from Pfam, Gene Ontology anonotations from GOA / AmiGO, structure based annotations from SCOP, PDB header data (see PDB File Format) and Uniprot description and accession IDs. Users should use proper keyword with proper target database for better results from the searches.


3DSwap - BLAST search:

Users can utilize 3DSwap BLAST interface to search the query sequence against curated hinge, swapped and full sequence database of proteins involved in 3D domain swapping. Searches against sequence of swapped structures are implemented in 3 levels. User can query the sequence against database of full set of sequences derived from structures in 3Dswap, search against the sequence curated from the swapped region or the hinge region. Full length sequence searches are implemented using normal BLASTP parameters, for hinge region the following parameters are used : word size (-W) is set to 2, Filter query sequence is set to F. PAM30 is used instead of BLOSUM62 to enable better search results from the hinge region searches.


3DSwap - Download:

Download section of 3DSwap provides PDB file, Quarternary assembly of the structure, hydrogen bond data using HBOND,secondary structure data using SSTRUC, structure accessibility using PSA and JOY .tem files.


References:


3DSwap Database Team :

Prof. R. Sowdhamini (Contact : mini@ncbs.res.in)
Khader Shameer, Prashant N Shingate, Manjunath SCP, Karthika M. G, Ganesan Pugalenthi and Prof. R. Sowdhamini