Sandbox Reserved 1103
From Proteopedia
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== Structure == | == Structure == | ||
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The [https://en.wikipedia.org/wiki/TERF1 TRF1] TRFH domain is a sequence motif of about 200 amino acids located in the centre of TRF1. It is entirely constituted of α helices and binds to another TRF1 TRFH to form a homodimer. The two monomers are antiparallel and form a homodimer which is symmetrical. There are three α-helices from each monomer involved in this homodimerization: <scene name='82/829356/Helices_1/1'>the helices 1</scene>, <scene name='82/829356/Helices_2/1'>2</scene> <scene name='82/829356/Helices_9/1'>9</scene>. To form a dimer, the helix 1 of one monomer comes into contact with helix 1 of the other monomer, its helix 2 does it with the helix 2, and so does the helix 9. The two helices 9 stabilize the dimer interface and are perpendicular to the helices 1, forming a cross brace at the top and the bottom of it. The two helices 1 are the core of the dimer interface. This interface involves many hydrophobic interactions and a few hydrogen bonds. The amino acids <scene name='82/829356/Trp77/3'>Trp77</scene> of each helix 1 are central to the formation of the hydrophobic core. “Trp77 packs against Phe255 (helix 9) within the monomer and between Ala259 and Ala260 and against Val263 of helix 9 from its partner” (Fairall L et al Mol Cell.<ref>PMID: 11545737</ref>) The hydrogen bonds involved in the dimer interface are formed between Glu71 of one monomer with Ser85 of the other monomer. Overall, this dimer interface is highly hydrophobic and packed. | The [https://en.wikipedia.org/wiki/TERF1 TRF1] TRFH domain is a sequence motif of about 200 amino acids located in the centre of TRF1. It is entirely constituted of α helices and binds to another TRF1 TRFH to form a homodimer. The two monomers are antiparallel and form a homodimer which is symmetrical. There are three α-helices from each monomer involved in this homodimerization: <scene name='82/829356/Helices_1/1'>the helices 1</scene>, <scene name='82/829356/Helices_2/1'>2</scene> <scene name='82/829356/Helices_9/1'>9</scene>. To form a dimer, the helix 1 of one monomer comes into contact with helix 1 of the other monomer, its helix 2 does it with the helix 2, and so does the helix 9. The two helices 9 stabilize the dimer interface and are perpendicular to the helices 1, forming a cross brace at the top and the bottom of it. The two helices 1 are the core of the dimer interface. This interface involves many hydrophobic interactions and a few hydrogen bonds. The amino acids <scene name='82/829356/Trp77/3'>Trp77</scene> of each helix 1 are central to the formation of the hydrophobic core. “Trp77 packs against Phe255 (helix 9) within the monomer and between Ala259 and Ala260 and against Val263 of helix 9 from its partner” (Fairall L et al Mol Cell.<ref>PMID: 11545737</ref>) The hydrogen bonds involved in the dimer interface are formed between Glu71 of one monomer with Ser85 of the other monomer. Overall, this dimer interface is highly hydrophobic and packed. | ||
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== Disease == | == Disease == | ||
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Since TIN2 is a protein part of the shelterin complex that regulate the length of telomere, a mutation of the TINF2 gene can lead to telomeropathies: | Since TIN2 is a protein part of the shelterin complex that regulate the length of telomere, a mutation of the TINF2 gene can lead to telomeropathies: | ||
[https://en.wikipedia.org/wiki/Dyskeratosis_congenita Dyskeratosis congenita] and [https://en.wikipedia.org/wiki/Revesz_syndrome Revesz syndrome] . | [https://en.wikipedia.org/wiki/Dyskeratosis_congenita Dyskeratosis congenita] and [https://en.wikipedia.org/wiki/Revesz_syndrome Revesz syndrome] . | ||
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=== Revesz syndrome === | === Revesz syndrome === | ||
| - | Revesz syndrome is characterise by bone marrow <ref>PMID: 17901676 </ref>. | + | Revesz syndrome is characterise by bone marrow <ref>PMID: 17901676 </ref>. Revesz syndrome is according to some researcher to be part of the DKC disease spectrum. Patients with Revesz syndrome have presented with heterozygous mutations in TINF2 gene which is located on chromosome 14q12. There is no treatment for this disease yet. |
| - | Revesz syndrome is according to some researcher to be part of the DKC disease spectrum. | + | |
== References == | == References == | ||
Revision as of 20:52, 14 January 2020
TRF1 TRFH domain and TIN2 peptide complex, pdb=3BQO
The TRFH (Telomeric Repeat Factor Homology) is a domain which is in the centre of the TRF1(Telomeric Repeat-Binding Factor) and of about 200 amino acids.In humans TERF1 is encoded by the TERF1 gene. TIN2(TERF1-interacting Nuclear Factor) is a protein encoded in humans by the TINF2 gene that can bind to TRFH TRF1.
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