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.

5tjb

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

I-II linker of TRPML1 channel at pH 4.5

Structural highlights

5tjb is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.4Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MCLN1_HUMAN Mucolipidosis type 4. The disease is caused by mutations affecting the gene represented in this entry.

Function

MCLN1_HUMAN Cation channel probably playing a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. Could play a major role in Ca(2+) transport regulating lysosomal exocytosis.^[1] ^[2]

Publication Abstract from PubMed

The activities of organellar ion channels are often regulated by Ca2+ and H+, which are present in high concentrations in many organelles. Here we report a structural element critical for dual Ca2+/pH regulation of TRPML1, a Ca2+-release channel crucial for endolysosomal function. TRPML1 mutations cause mucolipidosis type IV (MLIV), a severe lysosomal storage disorder characterized by neurodegeneration, mental retardation and blindness. We obtained crystal structures of the 213-residue luminal domain of human TRPML1 containing three missense MLIV-causing mutations. This domain forms a tetramer with a highly electronegative central pore formed by a novel luminal pore loop. Cysteine cross-linking and cryo-EM analyses confirmed that this architecture occurs in the full-length channel. Structure-function studies demonstrated that Ca2+ and H+ interact with the luminal pore and exert physiologically important regulation. The MLIV-causing mutations disrupt the luminal-domain structure and cause TRPML1 mislocalization. Our study reveals the structural underpinnings of TRPML1's regulation, assembly and pathogenesis.

Structural basis of dual Ca2+/pH regulation of the endolysosomal TRPML1 channel.,Li M, Zhang WK, Benvin NM, Zhou X, Su D, Li H, Wang S, Michailidis IE, Tong L, Li X, Yang J Nat Struct Mol Biol. 2017 Mar;24(3):205-213. doi: 10.1038/nsmb.3362. Epub 2017, Jan 23. PMID:28112729^[3]

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

References

↑ LaPlante JM, Falardeau J, Sun M, Kanazirska M, Brown EM, Slaugenhaupt SA, Vassilev PM. Identification and characterization of the single channel function of human mucolipin-1 implicated in mucolipidosis type IV, a disorder affecting the lysosomal pathway. FEBS Lett. 2002 Dec 4;532(1-2):183-7. PMID:12459486
↑ Raychowdhury MK, Gonzalez-Perrett S, Montalbetti N, Timpanaro GA, Chasan B, Goldmann WH, Stahl S, Cooney A, Goldin E, Cantiello HF. Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel. Hum Mol Genet. 2004 Mar 15;13(6):617-27. Epub 2004 Jan 28. PMID:14749347 doi:http://dx.doi.org/10.1093/hmg/ddh067
↑ Li M, Zhang WK, Benvin NM, Zhou X, Su D, Li H, Wang S, Michailidis IE, Tong L, Li X, Yang J. Structural basis of dual Ca2+/pH regulation of the endolysosomal TRPML1 channel. Nat Struct Mol Biol. 2017 Mar;24(3):205-213. doi: 10.1038/nsmb.3362. Epub 2017, Jan 23. PMID:28112729 doi:http://dx.doi.org/10.1038/nsmb.3362

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/5tjb"

@@ Line 1: / Line 1: @@
 ==I-II linker of TRPML1 channel at pH 4.5==
-<StructureSection load='5tjb' size='340' side='right' caption='[[5tjb]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+<StructureSection load='5tjb' size='340' side='right'caption='[[5tjb]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5tjb]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5TJB FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5tjb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TJB FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5tja|5tja]], [[5tjc|5tjc]]</td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</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=5tjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tjb OCA], [http://pdbe.org/5tjb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5tjb RCSB], [http://www.ebi.ac.uk/pdbsum/5tjb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5tjb ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tjb OCA], [https://pdbe.org/5tjb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tjb RCSB], [https://www.ebi.ac.uk/pdbsum/5tjb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tjb ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN]] Mucolipidosis type 4. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN] Mucolipidosis type 4. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN]] Cation channel probably playing a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. Could play a major role in Ca(2+) transport regulating lysosomal exocytosis.<ref>PMID:12459486</ref> <ref>PMID:14749347</ref>
+[https://www.uniprot.org/uniprot/MCLN1_HUMAN MCLN1_HUMAN] Cation channel probably playing a role in the endocytic pathway and in the control of membrane trafficking of proteins and lipids. Could play a major role in Ca(2+) transport regulating lysosomal exocytosis.<ref>PMID:12459486</ref> <ref>PMID:14749347</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Benvin, N M]]
+[[Category: Homo sapiens]]
-[[Category: Li, H]]
+[[Category: Large Structures]]
-[[Category: Li, M]]
+[[Category: Benvin NM]]
-[[Category: Li, X]]
+[[Category: Li H]]
-[[Category: Michailidis, I E]]
+[[Category: Li M]]
-[[Category: Su, D]]
+[[Category: Li X]]
-[[Category: Tong, L]]
+[[Category: Michailidis IE]]
-[[Category: Wang, S]]
+[[Category: Su D]]
-[[Category: Yang, J]]
+[[Category: Tong L]]
-[[Category: Zhang, W K]]
+[[Category: Wang S]]
-[[Category: Zhou, X]]
+[[Category: Yang J]]
-[[Category: Calcium and ph regulation]]
+[[Category: Zhang WK]]
-[[Category: Endolysosomal lumen]]
+[[Category: Zhou X]]
-[[Category: Tetramer]]
-[[Category: Transport protein]]

5tjb

From Proteopedia

Current revision

I-II linker of TRPML1 channel at pH 4.5

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox