Calcium pump

{{Short description|Family of transport proteins}} {{technical|date=January 2016}} '''Calcium pumps''' are a family of ion transporters found in the cell membrane of all animal cells. They are responsible for the active transport of calcium out of the cell for the maintenance of the steep Ca²⁺ electrochemical gradient across the cell membrane. Calcium pumps play a crucial role in proper cell signalling by keeping the intracellular calcium concentration roughly 10,000 times lower than the extracellular concentration.<ref name="Carafoli">{{cite journal |author=Carafoli E |title=Calcium pump of the plasma membrane |journal=Physiol. Rev. |volume=71 |issue=1 |pages=129–53 |date=January 1991 |pmid=1986387 |doi= 10.1152/physrev.1991.71.1.129}}</ref> Essentially, calcium pumps use energy to transport calcium across cell membranes, which allows the body to perform tasks that would otherwise be difficult to perform. Failure for the body to transport sufficient amounts of calcium is one cause of muscle cramps.

The plasma membrane Ca²⁺ ATPase and the sodium-calcium exchanger are together the main regulators of cytoplasmic Ca²⁺ concentrations.<ref name="Strehler ">{{cite journal |author=Strehler EE, Zacharias DA |title=Role of alternative splicing in generating isoform diversity among plasma membrane calcium pumps |journal=Physiol. Rev. |volume=81 |issue=1 |pages=21–50 |date=January 2001 |pmid=11152753 |doi= 10.1152/physrev.2001.81.1.21|s2cid=9062253 }}</ref>

== Biological role == {{main article|Calcium in biology}} Ca²⁺ has many important roles as an intracellular messenger. The release of a large amount of free Ca²⁺ can trigger a fertilized egg to develop, skeletal muscle cells to contract, secretion by secretory cells and interactions with Ca²⁺ -responsive proteins like calmodulin.<ref name="Alberts"/> To maintain low concentrations of free Ca²⁺ in the cytosol, cells use membrane pumps like calcium ATPase found in the membranes of sarcoplasmic reticulum of skeletal muscle. These pumps are needed to provide the steep electrochemical gradient that allows Ca²⁺ to rush into the cytosol when a stimulus signal opens the Ca²⁺ channels in the membrane. The pumps are also necessary to actively pump the Ca²⁺ back out of the cytoplasm and return the cell to its pre-signal state.<ref name="Alberts">{{cite book|last1=Alberts|first1=Bruce|last2=Bray|first2=Dennis|last3=Hopkin|first3=Karen|last4=Johnson|first4=Alexander D|last5=Lewis|first5=Julian|last6=Raff|first6=Martin|last7=Roberts|first7=Keith|last8=Walter|first8=Peter|title=Essential Cell Biology|date=2009|publisher=Garland Science|location=New York|isbn=978-0815341291|pages=552–554|edition=3rd}}<!--|accessdate=28 March 2016--></ref>

==Crystallography of calcium pumps== The structure of calcium pumps found in the sarcoplasmic reticulum of skeletal muscle was elucidated in 2000 by Toyoshima, et al. using microscopy of tubular crystals and 3D microcrystals. The pump has a molecular mass of 110,000 amu, shows three well separated cytoplasmic domains, with a transmembrane domain consisting of ten alpha helices and two transmembrane Ca²⁺ binding sites.<ref>{{cite journal|last1=Toyoshima|first1=Chikashi|last2=Nakasako|first2=Masayoshi|last3=Nomura|first3=Hiromi|last4=Ogawa|first4=Haruo|title=Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution|journal=Nature|date=8 June 2000|volume=405|issue=6787|pages=647–655|doi=10.1038/35015017|pmid=10864315|bibcode=2000Natur.405..647T|s2cid=4316039}}</ref>

==Mechanism== Classical theory of active transport for P-type ATPases <ref>{{cite journal|last1=Toyoshima|first1=Chikashi|last2=Norimatsu|first2=Yoshiyuki|last3=Iwasawa|first3=Shiho|last4=Tsuda|first4=Takeo|last5=Ogawa|first5=Haruo|title=How processing of aspartylphosphate is coupled to lumenal gating of the ion pathway in the calcium pump|journal=Proceedings of the National Academy of Sciences|date=5 December 2007|volume=104|issue=50|pages=19831–19836|doi=10.1073/pnas.0709978104|pmid=18077416|pmc=2148383|bibcode=2007PNAS..10419831T|doi-access=free}}</ref> {| class="wikitable" |- |E1 →||(2H⁺ out, 2Ca²⁺ in)→||E1⋅2Ca²⁺ →|| E1⋅ ATP |- | ↑ || || || ↓ |- |E2|| || || E1⋅ADP |- |↑(Pi out)|| || || ↓(ADP out) |- |E2⋅Pi||← E2P ||←(2H⁺ in, 2Ca²⁺ out) || ← E1P |} Data from crystallography studies by Chikashi Toyoshima applied to the above cycle <ref>{{cite journal|last1=Toyoshima|first1=Chikashi|last2=Nomura|first2=Hiromi|title=Structural changes in the calcium pump accompanying the dissociation of calcium|journal=Nature|date=8 August 2002|volume=418|issue=6898|pages=605–611|doi=10.1038/nature00944|pmid=12167852|bibcode=2002Natur.418..605T|s2cid=1441673}}</ref><ref>{{cite journal|last1=Toyoshima|first1=Chikashi|last2=Mizutani|first2=Tatsuaki|title=Crystal structure of the calcium pump with a bound ATP analogue|journal=Nature|date=30 June 2004|volume=430|issue=6999|pages=529–535|doi=10.1038/nature02680|pmid=15229613|bibcode=2004Natur.430..529T|s2cid=4331138}}</ref>

{| class="wikitable" |- | '''E1''' - high affinity for Ca²⁺, 2 Ca²⁺ bound, 2 H⁺ counter ions released |- | '''E1⋅2Ca²⁺''' - cytoplasmic gate open, free Ca²⁺ ion exchange occurs between bound ions and those in cytoplasm, closed configuration of '''N''', '''P''', '''A''' domains broken, exposing catalytic site |- | '''E1⋅ ATP''' - ATP binds and links '''N''' to '''P''', '''P''' bends, '''N''' contacts '''A''', '''A''' causes '''M1''' helix to pull up, closes cytoplasmic gate, bound Ca²⁺ occluded in transmembrane |- | '''E1⋅ADP''' - Phosphoryl transfer, ADP dissociates |- | '''E1P''' - '''A''' rotates, transmembrane helices rearrange, binding sites destroyed, lumenal gate opened, bound Ca²⁺ released |- | '''E2P''' - open ion pathway to lumen, Ca²⁺ to lumen |- | '''E2⋅Pi''' - '''A''' catalyzes release of the Pi, '''P''' unbends, transmembrane helices rearranged, closes lumenal gate |- | '''E2''' - transmembrane '''M1''' forms cytoplasmic access tunnel to Ca²⁺ binding sites |}

== References == {{Reflist|2}}

Category:Cell biology Category:Transport proteins

nl:Sarcolemmale calciumpomp