2dq5
From Proteopedia
(New page: 200px<br /> <applet load="2dq5" size="450" color="white" frame="true" align="right" spinBox="true" caption="2dq5" /> '''solution structure of the Mid1 B Box2 Chc(D...) |
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'''solution structure of the Mid1 B Box2 Chc(D/C)C2H2 Zinc-Binding Domain: insights into an evolutionary conserved ring fold'''<br /> | '''solution structure of the Mid1 B Box2 Chc(D/C)C2H2 Zinc-Binding Domain: insights into an evolutionary conserved ring fold'''<br /> | ||
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==Overview== | ==Overview== | ||
The B-box type 2 domain is a prominent feature of a large and growing, family of RING, B-box, coiled-coil (RBCC) domain-containing proteins and, is also present in more than 1500 additional proteins. Most proteins, usually contain a single B-box2 domain, although some proteins contain, tandem domains consisting of both type 1 and type 2 B-boxes, which, actually share little sequence similarity. Recently, we determined the, solution structure of B-box1 from MID1, a putative E3 ubiquitin ligase, that is mutated in X-linked Opitz G/BBB syndrome, and showed that it, adopted a betabetaalpha RING-like fold. Here, we report the tertiary, structure of the B-box2 (CHC(D/C)C(2)H(2)) domain from MID1 using, multidimensional NMR spectroscopy. This MID1 B-box2 domain consists of a, short alpha-helix and a structured loop with two short anti-parallel, beta-strands and adopts a tertiary structure similar to the B-box1 and, RING structures, even though there is minimal primary sequence similarity, between these domains. By mutagenesis, ESI-FTICR and ICP mass, spectrometry, we show that the B-box2 domain coordinates two zinc atoms, with a 'cross-brace' pattern: one by Cys175, His178, Cys195 and Cys198 and, the other by Cys187, Asp190, His204, and His207. Interestingly, this is, the first case that an aspartic acid is involved in zinc atom coordination, in a zinc-finger domain, although aspartic acid has been shown to, coordinate non-catalytic zinc in matrix metalloproteinases. In addition, the finding of a Cys195Phe substitution identified in a patient with, X-linked Opitz GBBB syndrome supports the importance of proper zinc, coordination for the function of the MID1 B-box2 domain. Notably, however, our structure differs from the only other published B-box2 structure, that, from XNF7, which was shown to coordinate one zinc atom. Finally, the, similarity in tertiary structures of the B-box2, B-box1 and RING domains, suggests these domains have evolved from a common ancestor. | The B-box type 2 domain is a prominent feature of a large and growing, family of RING, B-box, coiled-coil (RBCC) domain-containing proteins and, is also present in more than 1500 additional proteins. Most proteins, usually contain a single B-box2 domain, although some proteins contain, tandem domains consisting of both type 1 and type 2 B-boxes, which, actually share little sequence similarity. Recently, we determined the, solution structure of B-box1 from MID1, a putative E3 ubiquitin ligase, that is mutated in X-linked Opitz G/BBB syndrome, and showed that it, adopted a betabetaalpha RING-like fold. Here, we report the tertiary, structure of the B-box2 (CHC(D/C)C(2)H(2)) domain from MID1 using, multidimensional NMR spectroscopy. This MID1 B-box2 domain consists of a, short alpha-helix and a structured loop with two short anti-parallel, beta-strands and adopts a tertiary structure similar to the B-box1 and, RING structures, even though there is minimal primary sequence similarity, between these domains. By mutagenesis, ESI-FTICR and ICP mass, spectrometry, we show that the B-box2 domain coordinates two zinc atoms, with a 'cross-brace' pattern: one by Cys175, His178, Cys195 and Cys198 and, the other by Cys187, Asp190, His204, and His207. Interestingly, this is, the first case that an aspartic acid is involved in zinc atom coordination, in a zinc-finger domain, although aspartic acid has been shown to, coordinate non-catalytic zinc in matrix metalloproteinases. In addition, the finding of a Cys195Phe substitution identified in a patient with, X-linked Opitz GBBB syndrome supports the importance of proper zinc, coordination for the function of the MID1 B-box2 domain. Notably, however, our structure differs from the only other published B-box2 structure, that, from XNF7, which was shown to coordinate one zinc atom. Finally, the, similarity in tertiary structures of the B-box2, B-box1 and RING domains, suggests these domains have evolved from a common ancestor. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Opitz G syndrome, type I OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300552 300552]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2DQ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2DQ5 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DQ5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: zinc coordination]] | [[Category: zinc coordination]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:02:53 2008'' |
Revision as of 13:02, 23 January 2008
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solution structure of the Mid1 B Box2 Chc(D/C)C2H2 Zinc-Binding Domain: insights into an evolutionary conserved ring fold
Overview
The B-box type 2 domain is a prominent feature of a large and growing, family of RING, B-box, coiled-coil (RBCC) domain-containing proteins and, is also present in more than 1500 additional proteins. Most proteins, usually contain a single B-box2 domain, although some proteins contain, tandem domains consisting of both type 1 and type 2 B-boxes, which, actually share little sequence similarity. Recently, we determined the, solution structure of B-box1 from MID1, a putative E3 ubiquitin ligase, that is mutated in X-linked Opitz G/BBB syndrome, and showed that it, adopted a betabetaalpha RING-like fold. Here, we report the tertiary, structure of the B-box2 (CHC(D/C)C(2)H(2)) domain from MID1 using, multidimensional NMR spectroscopy. This MID1 B-box2 domain consists of a, short alpha-helix and a structured loop with two short anti-parallel, beta-strands and adopts a tertiary structure similar to the B-box1 and, RING structures, even though there is minimal primary sequence similarity, between these domains. By mutagenesis, ESI-FTICR and ICP mass, spectrometry, we show that the B-box2 domain coordinates two zinc atoms, with a 'cross-brace' pattern: one by Cys175, His178, Cys195 and Cys198 and, the other by Cys187, Asp190, His204, and His207. Interestingly, this is, the first case that an aspartic acid is involved in zinc atom coordination, in a zinc-finger domain, although aspartic acid has been shown to, coordinate non-catalytic zinc in matrix metalloproteinases. In addition, the finding of a Cys195Phe substitution identified in a patient with, X-linked Opitz GBBB syndrome supports the importance of proper zinc, coordination for the function of the MID1 B-box2 domain. Notably, however, our structure differs from the only other published B-box2 structure, that, from XNF7, which was shown to coordinate one zinc atom. Finally, the, similarity in tertiary structures of the B-box2, B-box1 and RING domains, suggests these domains have evolved from a common ancestor.
About this Structure
2DQ5 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Solution Structure of the MID1 B-box2 CHC(D/C)C(2)H(2) Zinc-binding Domain: Insights into an Evolutionarily Conserved RING Fold., Massiah MA, Matts JA, Short KM, Simmons BN, Singireddy S, Yi Z, Cox TC, J Mol Biol. 2007 May 25;369(1):1-10. Epub 2007 Mar 15. PMID:17428496
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