This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4nl9

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 08:27, 10 April 2019

Crystal structure of the human Anks3-SAM/Anks6-SAM heterodimer

Structural highlights

4nl9 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4nj8
Gene:	ANKS3, KIAA1977 (HUMAN), ANKRD14, ANKS6, PKDR1, SAMD6 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[ANKS6_HUMAN] Juvenile autosomal recessive medullary cystic kidney disease;Infantile autosomal recessive medullary cystic kidney disease. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

[ANKS6_HUMAN] Required for renal function.^[2]

Publication Abstract from PubMed

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure in humans. In the PKD/Mhm(cy/+) rat model of ADPKD, the point mutation R823W in the sterile alpha motif (SAM) domain of the protein ANKS6 is responsible for disease. SAM domains are known protein-protein interaction domains, capable of binding each other to form polymers and heterodimers. Despite its physiological importance, little is known about the function of ANKS6 and how the R823W point mutation leads to PKD. Recent work has revealed that ANKS6 interacts with a related protein called ANKS3. Both ANKS6 and ANKS3 have a similar domain structure, with ankyrin repeats at the N-terminus and a SAM domain at the C-terminus. RESULTS: The SAM domain of ANKS3 is identified as a direct binding partner of the ANKS6 SAM domain. We find that ANKS3-SAM polymerizes and ANKS6-SAM can bind to one end of the polymer. We present crystal structures of both the ANKS3-SAM polymer and the ANKS3-SAM/ANKS6-SAM complex, revealing the molecular details of their association. We also learn how the R823W mutation disrupts ANKS6 function by dramatically destabilizing the SAM domain such that the interaction with ANKS3-SAM is lost. CONCLUSIONS: ANKS3 is a direct interacting partner of ANKS6. By structurally and biochemically characterizing the interaction between the ANKS3 and ANKS6 SAM domains, our work provides a basis for future investigation of how the interaction between these proteins mediates kidney function.

Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3.,Leettola CN, Knight MJ, Cascio D, Hoffman S, Bowie JU BMC Struct Biol. 2014 Jul 7;14(1):17. PMID:24998259^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Hoff S, Halbritter J, Epting D, Frank V, Nguyen TM, van Reeuwijk J, Boehlke C, Schell C, Yasunaga T, Helmstadter M, Mergen M, Filhol E, Boldt K, Horn N, Ueffing M, Otto EA, Eisenberger T, Elting MW, van Wijk JA, Bockenhauer D, Sebire NJ, Rittig S, Vyberg M, Ring T, Pohl M, Pape L, Neuhaus TJ, Elshakhs NA, Koon SJ, Harris PC, Grahammer F, Huber TB, Kuehn EW, Kramer-Zucker A, Bolz HJ, Roepman R, Saunier S, Walz G, Hildebrandt F, Bergmann C, Lienkamp SS. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet. 2013 Aug;45(8):951-6. doi: 10.1038/ng.2681. Epub 2013 Jun 23. PMID:23793029 doi:http://dx.doi.org/10.1038/ng.2681
↑ Hoff S, Halbritter J, Epting D, Frank V, Nguyen TM, van Reeuwijk J, Boehlke C, Schell C, Yasunaga T, Helmstadter M, Mergen M, Filhol E, Boldt K, Horn N, Ueffing M, Otto EA, Eisenberger T, Elting MW, van Wijk JA, Bockenhauer D, Sebire NJ, Rittig S, Vyberg M, Ring T, Pohl M, Pape L, Neuhaus TJ, Elshakhs NA, Koon SJ, Harris PC, Grahammer F, Huber TB, Kuehn EW, Kramer-Zucker A, Bolz HJ, Roepman R, Saunier S, Walz G, Hildebrandt F, Bergmann C, Lienkamp SS. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet. 2013 Aug;45(8):951-6. doi: 10.1038/ng.2681. Epub 2013 Jun 23. PMID:23793029 doi:http://dx.doi.org/10.1038/ng.2681
↑ Leettola CN, Knight MJ, Cascio D, Hoffman S, Bowie JU. Characterization of the SAM domain of the PKD-related protein ANKS6 and its interaction with ANKS3. BMC Struct Biol. 2014 Jul 7;14(1):17. PMID:24998259 doi:http://dx.doi.org/10.1186/1472-6807-14-17

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4nl9"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human Anks3-SAM/Anks6-SAM heterodimer==
-<StructureSection load='4nl9' size='340' side='right' caption='[[4nl9]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
+<StructureSection load='4nl9' size='340' side='right'caption='[[4nl9]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4nl9]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NL9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NL9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4nl9]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4NL9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4NL9 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4nj8|4nj8]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ANKS3, KIAA1977 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), ANKRD14, ANKS6, PKDR1, SAMD6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4nl9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4nl9 OCA], [http://pdbe.org/4nl9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4nl9 RCSB], [http://www.ebi.ac.uk/pdbsum/4nl9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4nl9 ProSAT]</span></td></tr>
 </table>
@@ Line 25: / Line 26: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Bowie, J U]]
 [[Category: Cascio, D]]

4nl9

From Proteopedia

Revision as of 08:27, 10 April 2019

Crystal structure of the human Anks3-SAM/Anks6-SAM heterodimer

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox