View source for 7ulw


==CryoEM structure of human LACTB filament==
<StructureSection load='7ulw' size='340' side='right'caption='[[7ulw]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ulw]] is a 6 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=7ULW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ULW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1&#8491;</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=7ulw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ulw OCA], [https://pdbe.org/7ulw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ulw RCSB], [https://www.ebi.ac.uk/pdbsum/7ulw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ulw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LACTB_HUMAN LACTB_HUMAN] Mitochondrial serine protease that acts as a regulator of mitochondrial lipid metabolism (PubMed:28329758). Acts by decreasing protein levels of PISD, a mitochondrial enzyme that converts phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn), thereby affecting mitochondrial lipid metabolism (PubMed:28329758). It is unclear whether it acts directly by mediating proteolysis of PISD or by mediating proteolysis of another lipid metabolism protein (PubMed:28329758). Acts as a tumor suppressor that has the ability to inhibit proliferation of multiple types of breast cancer cells: probably by promoting decreased levels of PISD, thereby affecting mitochondrial lipid metabolism (PubMed:28329758).<ref>PMID:28329758</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mitochondria are complex organelles that play a central role in metabolism. Dynamic membrane-associated processes regulate mitochondrial morphology and bioenergetics in response to cellular demand. In tumor cells, metabolic reprogramming requires active mitochondrial metabolism for providing key metabolites and building blocks for tumor growth and rapid proliferation. To counter this, the mitochondrial serine beta-lactamase-like protein (LACTB) alters mitochondrial lipid metabolism and potently inhibits the proliferation of a variety of tumor cells. Mammalian LACTB is localized in the mitochondrial intermembrane space (IMS), where it assembles into filaments to regulate the efficiency of essential metabolic processes. However, the structural basis of LACTB polymerization and regulation remains incompletely understood. Here, we describe how human LACTB self-assembles into micron-scale filaments that increase their catalytic activity. The electron cryo-microscopy (cryoEM) structure defines the mechanism of assembly and reveals how highly ordered filament bundles stabilize the active state of the enzyme. We identify and characterize residues that are located at the filament-forming interface and further show that mutations that disrupt filamentation reduce enzyme activity. Furthermore, our results provide evidence that LACTB filaments can bind lipid membranes. These data reveal the detailed molecular organization and polymerization-based regulation of human LACTB and provide new insights into the mechanism of mitochondrial membrane organization that modulates lipid metabolism.

The structure of the human LACTB filament reveals the mechanisms of assembly and membrane binding.,Bennett JA, Steward LR, Rudolph J, Voss AP, Aydin H PLoS Biol. 2022 Dec 19;20(12):e3001899. doi: 10.1371/journal.pbio.3001899. , eCollection 2022 Dec. PMID:36534696<ref>PMID:36534696</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ulw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Aydin H]]
[[Category: Bennett JA]]
[[Category: Steward LR]]