Sodium-hydrogen exchange regulatory factor: Difference between revisions

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<StructureSection load='' size='340' side='right' caption='Human NHERF-1 second PDZ domain with CXCR2 peptide chimera (PDB cod [[4q3h]])' scene=''>
<StructureSection load='4q3h' size='340' side='right' caption='Human NHERF-1 second PDZ domain with CXCR2 peptide chimera (PDB cod [[4q3h]])' scene=''>




== Function ==
== Function ==


'''Sodium-hydrogen exchange regulatory factors''' (NHERF) are multifunctional adaptor protein which plays a role in the assembly of signal transduction complexes, linking ion channels and receptors to the actin skeleton<ref>PMID:11141479</ref>. NHERF-1 is the major isoform present in the brain and it regulates the trans-cellular ion transport through the blood-brain barrier membrane<ref>PMID:26010555</ref>.
'''Sodium-hydrogen exchange regulatory factors''' (NHERF) or '''ezrin-radixin-moesin binding phosphoprotein-50''' or '''PDZ domain-containing protein''' or '''Na+/H+ exchange regulatory cofactor NHE-RF1''' or '''NHERF''' are multifunctional adaptor protein which plays a role in the assembly of signal transduction complexes, linking ion channels and receptors to the actin skeleton<ref>PMID:11141479</ref>.  
* '''NHERF-1''' is the major isoform present in the brain and it regulates the trans-cellular ion transport through the blood-brain barrier membrane<ref>PMID:26010555</ref>.  It transduces cyclic AMP signals that inhibit the sodium-hydrogen exchanger present at the surface of kidney and gut<ref>PMID:12586353</ref>.  NHERF-1 contains 2 PDZ domains and one erm domain.
* '''NHERF-2''' is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling<ref>PMID:22343917</ref>.  NHERF-2 contains 2 PDZ domains and one erm domain.
*'''NHERF-3''' contains 4 PDZ domains no erm domain<ref>PMID:15905209</ref>.


== Relevance ==
== Relevance ==
Line 14: Line 17:
NHERF interacts with ion transporters and receptors via its PDZ domains and with the merlin, ezrin, radixin and moesin proteins via its c-terminal.  The CXCR2 peptide binds the second PDZ domain hydrophobic cleft<ref>PMID:26010555</ref>.
NHERF interacts with ion transporters and receptors via its PDZ domains and with the merlin, ezrin, radixin and moesin proteins via its c-terminal.  The CXCR2 peptide binds the second PDZ domain hydrophobic cleft<ref>PMID:26010555</ref>.


</StructureSection>
== 3D Structures of sodium-hydrogen exchange regulatory factor ==
== 3D Structures of sodium-hydrogen exchange regulatory factor ==
[[Sodium-hydrogen exchange regulatory factor 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
{{#tree:id=OrganizedByTopic|openlevels=0|
*Sodium-hydrogen exchange regulatory factor 1
**[[1g9o]], [[1gq5]] – hNHERF-1 PDZ 1 domain – human  <br />
**[[2m0t]] – hNHERF-1 PDZ 1 domain - NMR  <br />
**[[1i92]], [[4jl7]], [[4lmm]], [[4mpa]], [[4n6x]] - hNHERF-1 PDZ 1 domain/CFTR C-terminal peptide  <br />
**[[4pqw]] - hNHERF-1 PDZ 1 domain/phospholipase C peptide  <br />
**[[2m0u]] – hNHERF-1 PDZ 1 domain + CFTR C-terminal peptide - NMR  <br />
**[[2ozf]] – hNHERF-1 PDZ 2 domain <br />
**[[4q3h]] – hNHERF-1 PDZ 2 domain/CXCR2 peptide <br />
**[[2jxo]], [[2kjd]] – hNHERF-1 PDZ 2 domain - NMR  <br />
**[[2m0w]] – hNHERF-1 PDZ 2 domain + CFTR C-terminal peptide - NMR  <br />
**[[2krg]] – hNHERF-1 residues 150-358 - NMR  <br />
*Sodium-hydrogen exchange regulatory factor 2
**[[2ocs]] – hNHERF-2 PDZ 1 domain <br />
**[[2he4]] – hNHERF-2 PDZ 2 domain (mutant)<br />
*Sodium-hydrogen exchange regulatory factor 3 or PDZK1
**[[3ngh]] – mNHERF-3 PDZ 1 domain/HDL receptor - mouse<br />
**[[4f8k]] – mNHERF-3 PDZ 1 domain (mutant)/prostacyclin receptor<br />
**[[4q2p]] – hNHERF-3 PDZ 2 domain/phage peptide <br />
**[[3r68]] – mNHERF-3 PDZ 3 domain<br />
**[[3r69]] – mNHERF-3 PDZ 3 domain/HDL receptor<br />
**[[3tmh]] – hNHERF-3 PDZ 3 domain + CAMP-dependent protein kinase docking domain + AKAP-10 A-kinase-binding domain<br />
**[[4r2z]] – mNHERF-3 PDZ 4 domain <br />
}}
== References ==
== References ==
<references/>
<references/>
 
</StructureSection>
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 12:16, 13 August 2024


Function

Sodium-hydrogen exchange regulatory factors (NHERF) or ezrin-radixin-moesin binding phosphoprotein-50 or PDZ domain-containing protein or Na+/H+ exchange regulatory cofactor NHE-RF1 or NHERF are multifunctional adaptor protein which plays a role in the assembly of signal transduction complexes, linking ion channels and receptors to the actin skeleton[1].

  • NHERF-1 is the major isoform present in the brain and it regulates the trans-cellular ion transport through the blood-brain barrier membrane[2]. It transduces cyclic AMP signals that inhibit the sodium-hydrogen exchanger present at the surface of kidney and gut[3]. NHERF-1 contains 2 PDZ domains and one erm domain.
  • NHERF-2 is a negative regulator of endothelial proliferation and may have important roles in endothelial homeostasis and vascular modeling[4]. NHERF-2 contains 2 PDZ domains and one erm domain.
  • NHERF-3 contains 4 PDZ domains no erm domain[5].

Relevance

NHERF-1 inhibitors represent a potentially effective therapeutic approach to the treatment of hear failure[6]. NHERF-1 has a vital role in kidney cell survival[7]. NHERF are known to be involved in pathophysiologies of many brain diseases like epilepsy, Alzhheimer's disease, neuropathic pain and stroke.

Structural highlights

NHERF interacts with ion transporters and receptors via its PDZ domains and with the merlin, ezrin, radixin and moesin proteins via its c-terminal. The CXCR2 peptide binds the second PDZ domain hydrophobic cleft[8].

3D Structures of sodium-hydrogen exchange regulatory factor

Sodium-hydrogen exchange regulatory factor 3D structures

References

  1. ↑ Stemmer-Rachamimov AO, Wiederhold T, Nielsen GP, James M, Pinney-Michalowski D, Roy JE, Cohen WA, Ramesh V, Louis DN. NHE-RF, a merlin-interacting protein, is primarily expressed in luminal epithelia, proliferative endometrium, and estrogen receptor-positive breast carcinomas. Am J Pathol. 2001 Jan;158(1):57-62. doi: 10.1016/S0002-9440(10)63944-2. PMID:11141479 doi:http://dx.doi.org/10.1016/S0002-9440(10)63944-2
  2. ↑ Song S, Sun X, Li X, Yuan Y, Jiao N. Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization. Org Lett. 2015 Jun 19;17(12):2886-9. doi: 10.1021/acs.orglett.5b00932. Epub 2015 , May 26. PMID:26010555 doi:http://dx.doi.org/10.1021/acs.orglett.5b00932
  3. ↑ Weinman EJ, Steplock D, Shenolikar S. NHERF-1 uniquely transduces the cAMP signals that inhibit sodium-hydrogen exchange in mouse renal apical membranes. FEBS Lett. 2003 Feb 11;536(1-3):141-4. PMID:12586353 doi:10.1016/s0014-5793(03)00043-7
  4. ↑ Bhattacharya R, Wang E, Dutta SK, Vohra PK, E G, Prakash YS, Mukhopadhyay D. NHERF-2 maintains endothelial homeostasis. Blood. 2012 May 17;119(20):4798-806. PMID:22343917 doi:10.1182/blood-2011-11-392563
  5. ↑ Donowitz M, Cha B, Zachos NC, Brett CL, Sharma A, Tse CM, Li X. NHERF family and NHE3 regulation. J Physiol. 2005 Aug 15;567(Pt 1):3-11. PMID:15905209 doi:10.1113/jphysiol.2005.090399
  6. ↑ Morris K. Targeting the myocardial sodium-hydrogen exchange for treatment of heart failure. Expert Opin Ther Targets. 2002 Jun;6(3):291-8. doi: 10.1517/14728222.6.3.291 . PMID:12223070 doi:http://dx.doi.org/10.1517/14728222.6.3.291
  7. ↑ Parker MD, Myers EJ, Schelling JR. Na+-H+ exchanger-1 (NHE1) regulation in kidney proximal tubule. Cell Mol Life Sci. 2015 Jun;72(11):2061-74. doi: 10.1007/s00018-015-1848-8. Epub , 2015 Feb 14. PMID:25680790 doi:http://dx.doi.org/10.1007/s00018-015-1848-8
  8. ↑ Song S, Sun X, Li X, Yuan Y, Jiao N. Efficient and Practical Oxidative Bromination and Iodination of Arenes and Heteroarenes with DMSO and Hydrogen Halide: A Mild Protocol for Late-Stage Functionalization. Org Lett. 2015 Jun 19;17(12):2886-9. doi: 10.1021/acs.orglett.5b00932. Epub 2015 , May 26. PMID:26010555 doi:http://dx.doi.org/10.1021/acs.orglett.5b00932

Human NHERF-1 second PDZ domain with CXCR2 peptide chimera (PDB cod 4q3h)

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