2d10

Crystal structure of the Radixin FERM domain complexed with the NHERF-1 C-terminal tail peptideCrystal structure of the Radixin FERM domain complexed with the NHERF-1 C-terminal tail peptide

Structural highlights

2d10 is a 8 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1gc7, 1gc6, 1j19, 1isn, 2d11
Resources:	FirstGlance, OCA, RCSB, PDBsum

Disease

[NHERF_HUMAN] Defects in SLC9A3R1 are the cause of hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) [MIM:612287]. Hypophosphatemia results from idiopathic renal phosphate loss. It contributes to the pathogenesis of hypophosphatemic urolithiasis (formation of urinary calculi) as well to that of hypophosphatemic osteoporosis (bone demineralization).^[1] ^[2]

Function

[RADI_MOUSE] Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane. [NHERF_HUMAN] Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for recycling of internalized ADRB2. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. May enhance Wnt signaling. May participate in HTR4 targeting to microvilli (By similarity). Involved in the regulation of phosphate reabsorption in the renal proximal tubules.^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Na+/H+ exchanger regulatory factor (NHERF) is a key adaptor protein involved in the anchoring of ion channels and receptors to the actin cytoskeleton through binding to ERM (ezrin/radixin/moesin) proteins. NHERF binds the FERM domain of ERM proteins, although NHERF has no signature Motif-1 sequence for FERM binding found in adhesion molecules. The crystal structures of the radixin FERM domain complexed with the NHERF-1 and NHERF-2 C-terminal peptides revealed a peptide binding site of the FERM domain specific for the 13 residue motif MDWxxxxx(L/I)Fxx(L/F) (Motif-2), which is distinct from Motif-1. This Motif-2 forms an amphipathic alpha helix for hydrophobic docking to subdomain C of the FERM domain. This docking causes induced-fit conformational changes in subdomain C and affects binding to adhesion molecule peptides, while the two binding sites are not overlapped. Our studies provide structural paradigms for versatile ERM linkages between membrane proteins and the cytoskeleton.

Structural basis for NHERF recognition by ERM proteins.,Terawaki S, Maesaki R, Hakoshima T Structure. 2006 Apr;14(4):777-89. PMID:16615918^[7]

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

References

↑ Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prie D. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 2008 Sep 11;359(11):1128-35. PMID:18784102 doi:359/11/1128
↑ Courbebaisse M, Leroy C, Bakouh N, Salaun C, Beck L, Grandchamp B, Planelles G, Hall RA, Friedlander G, Prie D. A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism. PLoS One. 2012;7(4):e34764. doi: 10.1371/journal.pone.0034764. Epub 2012 Apr 10. PMID:22506049 doi:10.1371/journal.pone.0034764
↑ Murthy A, Gonzalez-Agosti C, Cordero E, Pinney D, Candia C, Solomon F, Gusella J, Ramesh V. NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. J Biol Chem. 1998 Jan 16;273(3):1273-6. PMID:9430655
↑ Yun CH, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, Weinman EJ, Donowitz M. cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3010-5. PMID:9096337
↑ Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M. A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. PMID:10499588 doi:10.1038/45816
↑ Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prie D. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 2008 Sep 11;359(11):1128-35. PMID:18784102 doi:359/11/1128
↑ Terawaki S, Maesaki R, Hakoshima T. Structural basis for NHERF recognition by ERM proteins. Structure. 2006 Apr;14(4):777-89. PMID:16615918 doi:10.1016/j.str.2006.01.015

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OCA

[1] Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prie D. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 2008 Sep 11;359(11):1128-35. PMID:18784102 doi:359/11/1128

[2] Courbebaisse M, Leroy C, Bakouh N, Salaun C, Beck L, Grandchamp B, Planelles G, Hall RA, Friedlander G, Prie D. A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism. PLoS One. 2012;7(4):e34764. doi: 10.1371/journal.pone.0034764. Epub 2012 Apr 10. PMID:22506049 doi:10.1371/journal.pone.0034764

[3] Murthy A, Gonzalez-Agosti C, Cordero E, Pinney D, Candia C, Solomon F, Gusella J, Ramesh V. NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common interactor for merlin and ERM (MERM) proteins. J Biol Chem. 1998 Jan 16;273(3):1273-6. PMID:9430655

[4] Yun CH, Oh S, Zizak M, Steplock D, Tsao S, Tse CM, Weinman EJ, Donowitz M. cAMP-mediated inhibition of the epithelial brush border Na+/H+ exchanger, NHE3, requires an associated regulatory protein. Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3010-5. PMID:9096337

[5] Cao TT, Deacon HW, Reczek D, Bretscher A, von Zastrow M. A kinase-regulated PDZ-domain interaction controls endocytic sorting of the beta2-adrenergic receptor. Nature. 1999 Sep 16;401(6750):286-90. PMID:10499588 doi:10.1038/45816

[6] Karim Z, Gerard B, Bakouh N, Alili R, Leroy C, Beck L, Silve C, Planelles G, Urena-Torres P, Grandchamp B, Friedlander G, Prie D. NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 2008 Sep 11;359(11):1128-35. PMID:18784102 doi:359/11/1128

[7] Terawaki S, Maesaki R, Hakoshima T. Structural basis for NHERF recognition by ERM proteins. Structure. 2006 Apr;14(4):777-89. PMID:16615918 doi:10.1016/j.str.2006.01.015

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2d10

Crystal structure of the Radixin FERM domain complexed with the NHERF-1 C-terminal tail peptideCrystal structure of the Radixin FERM domain complexed with the NHERF-1 C-terminal tail peptide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

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2d10

Crystal structure of the Radixin FERM domain complexed with the NHERF-1 C-terminal tail peptideCrystal structure of the Radixin FERM domain complexed with the NHERF-1 C-terminal tail peptide

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

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