Motifs and Domains in Proteins_exp_.pptx

Proteins Motifs and Domains Types of Motifs and Domains;
Functions of Motifs and Domains; databases for motifs and domains elucidation

1. Motifs and Domains Presented By: Maliha Rashid M.Phil Biotechnology UIBB, PMAS Arid Agriculture University Rawalpindi, Pakistan 1

2. Motifs small regions of protein three-dimensional structure or amino acid sequence shared among different proteins. Signatures of protein families and can often be used as tools for the prediction of protein function. They are recognizable regions of protein structure that may (or may not) be defined by a unique chemical or biological function. can’t exist independently 2

3. Motifs – Supersecondary Structures Supersecondary structure  refers to a combination of secondary structure elements, such as beta-alpha-beta  units helix-turn-helix motif also referred to as structural motifs 3

4. Function of motifs Describe short amino acid arrangements that are shared by protein family members Designed to be used in conjugation with protein sequence databases to assign putative functions to unknown proteins 4

5. Common Structural Motifs Alpha-loop-Alpha Beta-hairpin or beta-turn Greek Key Beta-Alpha-Beta 5

6. Alpha-loop-Alpha These are found in DNA-binding proteins that regulate transcription and also in calcium-binding proteins, in which the motif is often called the EF hand. The loop region in calcium-binding proteins is enriched in Asp, Glu, Ser, and Thr . Basic helix-turn-helix from the c- Myc protein (1NKP) 6

7. Beta-hairpin or beta-turn This motif is present in most antiparallel beta structures, both as an isolated ribbon and as part of beta sheets connected through a loop 7

8.  2D homology map of beta-hairpin from bovine pancreatic trypsin inhibitor (1k6u) 8

9. Greek Key The "Greek Key" symbol represents infinity and the eternal flow of things and resembles in part primitive keys. The Greek Key motif in proteins can be seen in the structure of antiparallel beta sheets in the ordering of four adjacent antiparallel beta strands Greek Key Motif 9

10. Figure shows a partial 2D topology map of Staphylococcus nuclease (2SNS) Greek Key motif from Staphylococcus nuclease (2SNS) 10

11. Beta-Alpha-Beta The motif is a common way to connect two  parallel  beta strands as compared to beta hairpins, which are used to connect antiparallel beta strands. Beta alpha beta motif from triose phosphate isomerase (1amk) 11

12. Larger Structural Motifs - Protein Architecture The Rossman Fold The TIM barrel ( triose-phosphate isomerase ), also known as an alpha/beta barrel. Beta Helices Beta Propellors 12

13. The Rossman Fold Structural motifs can serve particular functions within proteins such as enabling the binding of substrates or cofactors. For example, the Rossmann fold is responsible for binding to nucleotide cofactors such as nicotinamide adenine dinucleotide (NAD + ). composed of six parallel beta strands that form an extended beta sheet The first three strands are connected by α-helices resulting in a beta-alpha-beta-alpha-beta structure. Overall, the strands are arranged in the order of 321456 (1 = N-terminal, 6 = C-terminal). Five stranded Rossmann -like folds are arranged in the sequential order 32145.   The overall tertiary structure of the fold resembles a three-layered sandwich. 13

14. Cartoon diagram of the Rossmann Fold (helices A-F red and strands 1-6 yellow) from  E. coli  malate dehydrogenase enzyme. Schematic diagram of the six stranded Rossmann fold 14

15. Continued…. One of the features of the Rossmann fold is its co-factor binding specificity The most conserved segment of Rossmann folds is the first beta-alpha-beta segment Since this segment is in contact with the ADP portion of dinucleotides such as FAD, NAD and NADP it is also called as an " ADP-binding beta-beta fold" 15

16. Databases and software to predict/find motifs Motifscan InterProScan PROSITE Pfam Scan (http://pfam-legacy.xfam.org/) 16

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21. What Are Domains? distinct functional and structural units in a protein region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest are regions of a protein that has a specific function a compact folded three-dimensional structure 50 amino acids to 250 amino acids in length 21

22. Continued…   Often has sequence or structural resemblance to other protein structures or domains  fundamental units of tertiary structure each domain containing an individual hydrophobic core built from secondary structural units connected by loop regions 22

23. Examples of domains Zinc fingers are an example of small protein domains – a common DNA binding domain consists of ∼30 amino acids that may recognize three base pairs of DNA can recognize and bind to a specific DNA into the genome 23

24. Example: pyruvate kinase all-β nucleotide binding domain (in blue) an α/β-substrate binding domain (in grey) an α/β-regulatory domain (in olive green) Each domain in this protein occurs in diverse sets of  protein families 24

25. Types 1. α category domains consist almost entirely of α helices and loops 2. Β category consist only β sheets and loops/ Ββ turns 3. α / β category domains have super secondary such structures such as the βαβ motif 4. α + β category domains consist of local clusters of a helices and β sheet (where each type of structure arises from separate contiguous regions in the polypeptide chain 25

26. Significance of Domains D omain are independently stable, DOMAINS can be ‘swapped’ by genetic engineering between one proteins and another to make chimeric protein Metabolic Engineering can be placed by altering protein domain. Better analysis of protein, which will help in better understanding of the different domain causing different function in protein . 26

27. Domain databases PROSITE-Profile PfmaA PRINTs PRODOM SMART COGs TIGRFAM BLOCKs 27

28. Domain Servers The three major domain servers are used to make complete analyses of the domain contained in sequence InterProScan CD-Search Motif-Scan 28

29. References https://bio.libretexts.org/Workbench/Biochem_Remix_Acevedo/04%3A_The_Three-Dimensional_Structure_of_Proteins/4.03%3A_Secondary_Structural_Motifs_and_Domains https ://bio.libretexts.org/Bookshelves/Cell_and_Molecular_Biology/Book%3A_Basic_Cell_and_Molecular_Biology_(Bergtrom)/ 03%3A_Details_of_Protein_Structure/3.06%3A_Protein_Domains_Motifs_and_Folds_in_Protein_Structure https://bio.libretexts.org/Under_Construction/Cell_and_Molecular_Biology_(Bergtrom)/ 03%3A_Details_of_Protein_Structure/3.05%3A_Domains_Motifs_and_Folds_in_Protein_Structure https://www.ncbi.nlm.nih.gov/books/NBK26830 / 29