1bzk: Difference between revisions
New page: left|200px<br /> <applet load="1bzk" size="450" color="white" frame="true" align="right" spinBox="true" caption="1bzk" /> '''STRUCTURAL STUDIES ON THE EFFECTS OF THE DE... |
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'''STRUCTURAL STUDIES ON THE EFFECTS OF THE DELETION IN THE RED CELL ANION EXCHANGER (BAND3, AE1) ASSOCIATED WITH SOUTH EAST ASIAN OVALOCYTOSIS.'''<br /> | '''STRUCTURAL STUDIES ON THE EFFECTS OF THE DELETION IN THE RED CELL ANION EXCHANGER (BAND3, AE1) ASSOCIATED WITH SOUTH EAST ASIAN OVALOCYTOSIS.'''<br /> | ||
==Overview== | ==Overview== | ||
We have carried out a solution-state NMR study of synthetic peptides | We have carried out a solution-state NMR study of synthetic peptides patterned on the first membrane span of normal human band 3, and the same region of the mutant band 3 present in Southeast Asian ovalocytosis (SAO) which has a nine amino acid deletion. In 1:1 (v/v) chloroform/methanol, the 42 residue normal peptide (R389-K430) consisted of three helical regions. The slow solvent exchange of backbone amide protons revealed the helix from P403 to A416 was more stable than the "cytoplasmic" N-terminal helix from P391 to A400. These helices were separated by a sharp bend at P403, which is probably located at the boundary between the cytoplasmic domain and the first transmembrane span. The SAO deletion (A400-A408) removed the bend at P403, to leave a stable helix from P391 to A416 containing the residuum of the normal first transmembrane helix and with a hydrophobic turn replaced by a polar turn in the SAO peptide. Insertion of fragments of normal band 3 and band 3 SAO into microsomal membranes was investigated using a cell free translation system. A fragment composed of the cytoplasmic domain and the putative first membrane domain of normal band 3 (B3(1)) inserted stably into the membrane. However, the corresponding fragment of band 3 SAO [SAO(1)] did not integrate stably into membranes. Our results suggest that in SAO band 3, the region of the first membrane span of normal band 3 does not integrate properly into the membrane because it lacks a sufficiently long hydrophobic segment, and the deletion also disrupts a conserved structural subdomain at the membrane surface. | ||
==Disease== | ==Disease== | ||
Known diseases associated with this structure: | Known diseases associated with this structure: Blood group, Diego OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Blood group, Froese , OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Blood group, Waldner OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Blood group, Wright OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Diabetes insipidus, nephrogenic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300538 300538]], Hemolytic anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Malaria, resistance to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Nephrogenic syndrome of inappropriate antidiuresis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300538 300538]], Ovalocytosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Renal tubular acidosis, distal, AD OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Renal tubular acidosis, distal, AR OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]], Spherocytosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=109270 109270]] | ||
==About this Structure== | ==About this Structure== | ||
1BZK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with ACE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1BZK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BZK OCA]. | ||
==Reference== | ==Reference== | ||
Structural studies on the effects of the deletion in the red cell anion exchanger (band 3, AE1) associated with South East Asian ovalocytosis., Chambers EJ, Bloomberg GB, Ring SM, Tanner MJ, J Mol Biol. 1999 Jan 22;285(3):1289-307. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9887277 9887277] | Structural studies on the effects of the deletion in the red cell anion exchanger (band 3, AE1) associated with South East Asian ovalocytosis., Chambers EJ, Bloomberg GB, Ring SM, Tanner MJ, J Mol Biol. 1999 Jan 22;285(3):1289-307. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9887277 9887277] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bloomberg, G | [[Category: Bloomberg, G B.]] | ||
[[Category: Chambers, E | [[Category: Chambers, E J.]] | ||
[[Category: Ring, S | [[Category: Ring, S M.]] | ||
[[Category: Tanner, M | [[Category: Tanner, M J.A.]] | ||
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: human erythrocyte anion transporter]] | [[Category: human erythrocyte anion transporter]] | ||
| Line 26: | Line 25: | ||
[[Category: transmembrane]] | [[Category: transmembrane]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:00:52 2008'' | ||
Revision as of 13:00, 21 February 2008
|
STRUCTURAL STUDIES ON THE EFFECTS OF THE DELETION IN THE RED CELL ANION EXCHANGER (BAND3, AE1) ASSOCIATED WITH SOUTH EAST ASIAN OVALOCYTOSIS.
OverviewOverview
We have carried out a solution-state NMR study of synthetic peptides patterned on the first membrane span of normal human band 3, and the same region of the mutant band 3 present in Southeast Asian ovalocytosis (SAO) which has a nine amino acid deletion. In 1:1 (v/v) chloroform/methanol, the 42 residue normal peptide (R389-K430) consisted of three helical regions. The slow solvent exchange of backbone amide protons revealed the helix from P403 to A416 was more stable than the "cytoplasmic" N-terminal helix from P391 to A400. These helices were separated by a sharp bend at P403, which is probably located at the boundary between the cytoplasmic domain and the first transmembrane span. The SAO deletion (A400-A408) removed the bend at P403, to leave a stable helix from P391 to A416 containing the residuum of the normal first transmembrane helix and with a hydrophobic turn replaced by a polar turn in the SAO peptide. Insertion of fragments of normal band 3 and band 3 SAO into microsomal membranes was investigated using a cell free translation system. A fragment composed of the cytoplasmic domain and the putative first membrane domain of normal band 3 (B3(1)) inserted stably into the membrane. However, the corresponding fragment of band 3 SAO [SAO(1)] did not integrate stably into membranes. Our results suggest that in SAO band 3, the region of the first membrane span of normal band 3 does not integrate properly into the membrane because it lacks a sufficiently long hydrophobic segment, and the deletion also disrupts a conserved structural subdomain at the membrane surface.
DiseaseDisease
Known diseases associated with this structure: Blood group, Diego OMIM:[109270], Blood group, Froese , OMIM:[109270], Blood group, Waldner OMIM:[109270], Blood group, Wright OMIM:[109270], Diabetes insipidus, nephrogenic OMIM:[300538], Hemolytic anemia OMIM:[109270], Malaria, resistance to OMIM:[109270], Nephrogenic syndrome of inappropriate antidiuresis OMIM:[300538], Ovalocytosis OMIM:[109270], Renal tubular acidosis, distal, AD OMIM:[109270], Renal tubular acidosis, distal, AR OMIM:[109270], Spherocytosis OMIM:[109270]
About this StructureAbout this Structure
1BZK is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural studies on the effects of the deletion in the red cell anion exchanger (band 3, AE1) associated with South East Asian ovalocytosis., Chambers EJ, Bloomberg GB, Ring SM, Tanner MJ, J Mol Biol. 1999 Jan 22;285(3):1289-307. PMID:9887277
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