User:Adam Meade/Sandbox 1
From Proteopedia
Iron Response Regulator (Irr)
Contents |
Background Information
Iron is potentially toxic to cells, as in the presence of oxygen, Fenton reactions can produce reactive oxygen species that can destroy essential biomolecules. Balancing the amount of iron in the cell is important and this importance is apparent from the elaborate mechanisms cells devote to iron homeostasis. Part of this iron balancing is achieved by regulation of iron import. The genes required for ferric citrate transport in Rhodobacter sphaeroides form a cluster in the order fecI-fecR-fecABCDE, encoding a specialized sigma factor and a putative anti-sigma factor that together are responsible for regulated transcription of the ferric citrate transport operon, encoding an ABC-type ferric citrate transporter. In Escherichia coli, fecI transcription is regulated by Fur in response to iron availability; in Bradyrhizobium japonicum, as well as R. sphaeroides, which both lack Fur, fecI transcription is thought to be regulated by another iron-responsive DNA binding protein, Irr, or the iron response regulator protein, which can also be considered to be a relative to the family of Fur proteins. [1]
Irr and Other Iron-Regulating Proteins
Since there are bacteria that have to have iron level-mediating proteins present but do not have the Fur (ferric uptake regulator) protein, there must be another protein that takes its place. In the case of B. japonicum, which does not have the Fur protein, the Irr protein was found to be the regulator of iron levels within the cell.[2]
Function of Irr
Irr behaves differently than other regulatory proteins. To prevent the accumulation of toxic porphyrin precursors under iron limitation, as when iron is limiting, heme cannot be produced. [3]
Irr accumulates in cells under iron limitation, with very low levels of Irr being present in iron-replete cells. This is a distinction when compared to other Fur family proteins because it functions in the absence of the regulatory metal, whereas the other members require direct metal-binding for the protein to be activated. [4]
Phylogenetic Tree
http://consurf.tau.ac.il/results/1240766462/treeView.html
Chemical and Physical Properties of Irr
Molecular weight: 18338.8 Da
Theoretical pI: 6.03
| Amino Acid | Number present | Percentage of total present |
|---|---|---|
| Ala (A) | 15 | 9.2% |
| Arg (R) | 10 | 6.1% |
| Asn (N) | 6 | 3.7% |
| Asp (D) | 10 | 6.1% |
| Cys (C) | 1 | 0.6% |
| Gln (Q) | 5 | 3.1% |
| Glu (E) | 11 | 6.7% |
| Gly (G) | 9 | 5.5% |
| His (H) | 10 | 6.1% |
| Ile (I) | 3 | 1.8% |
| Leu (L) | 21 | 12.9% |
| Lys (K) | 6 | 3.7% |
| Met (M) | 6 | 3.7% |
| Phe (F) | 2 | 1.2% |
| Pro (P) | 8 | 4.9% |
| Ser (S) | 7 | 4.3% |
| Thr (T) | 13 | 8.0% |
| Trp (W) | 2 | 1.2% |
| Tyr (Y) | 6 | 3.7% |
| Val (V) | 12 | 7.4% |
| Pyl (O) | 0 | 0.0% |
| Sec (U) | 0 | 0.0% |
Evolution of Irr/Fur
Amino Acid Conservation Scores
The following are scores on how well conserved the amino acids are in relation to proteins with a similar structure to Irr. This could potentially show us where Irr evolved from/what Irr will evolve into.
- POS: The position of the AA in the SEQRES derived sequence.
- SEQ: The SEQRES derived sequence in one letter code.
- COLOR: The color scale representing the conservation scores (9 - conserved, 1 - variable).
- RESIDUE VARIETY: The residues variety at each position of the multiple sequence alignment.
POS SEQ COLOR RESIDUE VARIETY (normalized) 1 D 9 D 2 V 2* F,N,V,Y 3 N 6 A,N,S,T 4 E 3* E,G,K,Q,S,T 5 M 3* A,E,I,L,M,Q,T 6 L 9 L 7 Q 7 K,Q,R 8 S 1 D,E,K,N,Q,R,S,T 9 A 5 A,G,I,M,N,S,T,V 10 G 8 D,G 11 L 8 I,L,V 12 R 8 K,R 13 P 4 A,I,P,V,Y 14 T 9 T 15 R 3* E,F,G,K,L,P,R,V 16 Q 8 P,Q 17 R 9 R 18 M 3* E,H,I,L,M,Q,V 19 A 8 A,K,T,V 20 L 7 I,L,V 21 G 6 G,I,L,M 22 W 1 A,D,E,K,N,Q,R,W 23 L 1 A,F,I,L,M,T,V,Y 24 L 7 F,L,M,V 25 F 1 D,E,F,I,K,N,Q,R,V,Y 26 G 1 A,E,G,H,K,N,Q,S,T 27 K 3* A,E,H,K,P,S,T 28 G 1 A,D,E,G,H,K,M,P,R 29 A 1 A,C,E,G,L,M,N,Q,S,T 30 R 1 E,H,Q,R 31 H 9 H 32 L 3* A,F,I,L,M,P,V,Y 33 T 8 D,E,S,T 34 A 9 A,P,T 35 E 8 D,E 36 M 3* A,D,E,H,M,S,T 37 L 5 C,I,L,V 38 Y 7 F,I,Y 39 E 5 E,G,K,M,N,Q,R 40 E 1 A,E,H,I,K,L,R 41 A 6 A,F,I,L,V 42 T 2 A,E,I,L,M,R,S,T 43 L 1 A,D,E,F,G,L,N,P,S,V 44 A 1 A,D,E,I,K,L,M,P,Q,R,S 45 K 1 D,F,G,H,K,L,N,S 46 V 3* C,E,L,M,P,S,V 47 P 4 D,E,N,P 48 V 7 I,M,V 49 S 9 G,S 50 L 5 H,I,L,R,V 51 A 9 A,Q,S 52 T 9 A,T 53 V 8 I,V 54 Y 9 Y 55 N 8 D,N,R 56 T 8 N,T,V,X 57 L 9 L 58 N 7 H,K,N,R,T 59 Q 7 A,L,Q,V 60 L 7 F,L,M 61 T 5 A,D,E,K,R,T 62 D 4 A,D,E,Q,R,S 63 A 7 A,I,M,S,V 64 G 8 E,G,H 65 L 6 I,L,M 66 L 7 L,V 67 R 4 I,K,L,Q,R,S,T,V 68 Q 6 E,K,Q,R,S 69 V 5 H,I,L,N,S,V 70 S 5 D,H,N,P,Q,S,T 71 V 5 F,L,P,V,Y 72 D 2 A,D,E,G,S,T 73 G 5 D,E,G,S,T 74 T 5 A,D,G,N,S,T 75 K 5 G,H,K,S,V 76 T 6 A,K,S,T 77 Y 6 H,I,K,R,V,Y 78 F 6 F,Y 79 D 8 D,E 80 T 6 F,L,S,T 81 N 3 A,D,N,R,S,T,V 82 V 4* Q,V 83 T 1 D,E,K,N,P,Q,T,V 84 T 1 D,G,K,L,N,Q,S,T 85 H 1 D,E,G,H,K,P,S 86 H 8 D,E,H,N 87 H 9 H 88 Y 8 D,H,Y 89 Y 9 H,Y 90 L 2 A,I,L,M,V 91 E 1 E,K,L,M,T,V 92 N 2* D,E,K,N,Q,V 93 S 7 C,S,T 94 H 5 G,H,N,S 95 E 6 E,K,T 96 L 8 I,L,V 97 V 6 F,I,T,V 98 D 8 D,E 99 I 8 F,I 100 E 1 E,H,K,M,Q,S,T 101 D 6 D,N,S,Y 102 P 6 A,E,N,P 103 H 1 D,E,G,H,I,Q,V 104 L 8 I,L 105 A 3* A,K,Q 106 L 5* L,R 107 S 7 Q,S 108 K 3* D,K,R 109 M 4* E,K,M 110 P 7 I,P 111 E 4* A,E,S,V 112 V 2* A,E,R,V 113 P 3* E,K,P,Q 114 E 1 E,H,N,R,Y 115 G 7 G,N 116 Y 2 F,I,V,Y 117 E 5* E,R 118 I 6* I,L 119 A 6* A,V 120 R 4* D,R 121 I 4* H,I 122 D 6* D,N 123 M 6* L,M 124 V 8* V 125 V 5* L,V 126 R 4* R,Y 127 L 6* L,V 128 R 8* R 129 K 8* K 130 K 8* K 131 R 6* K,R
Structure of the Proposed Irr Protein
|
| Amino Terminus | Carboxy Terminus |
The amino acid sequence used to derive the structure shown is as follows:
1 msentaphhd ddvhaaalls grqpaltgcp whdvnemlqs aglrptrqrm algwllfgkg
61 arhltaemly eeatlakvpv slatvyntln qltdagllrq vsvdgtktyf dtnvtthhhy
121 ylenshelvd iedphlalsk mpevpegyei aridmvvrlr kkr
References
- ↑ Hamza I, S. Chauhan, R. Hassett, M. R. O'Brian, 1998. The bacterial irr protein is required for coordination of heme biosynthesis with iron availability.. Journal of Biological Chemistry 34:21669-74.
- ↑ Small, S. K., S. Puri, and M. R. O’Brian. 2009. Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria. Biometals 22:89-97.
- ↑ Small, S. K., S. Puri, and M. R. O’Brian. 2009. Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria. Biometals 22:89-97.
- ↑ Small, S. K., S. Puri, and M. R. O’Brian. 2009. Heme-dependent metalloregulation by the iron response regulator (Irr) protein in Rhizobium and other alpha-proteobacteria. Biometals 22:89-97.
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