Aquaporins

Aquaporins

Aditya(09026)5th Year BS-MSIISER BHOPAL

What is Aquaporin ??

• Aquaporin is a 28 kDa protein embedded in the cell membrane in order to regulate the flow of water

• presence of these water channels increases the permeability to water of the cell membrane

• Thousands of millions of water molecules per second pass through one single channel

• Found in all kingdoms of life including bacteria, plants, and mammals

• 13 in mammals, 6 in kidney• In plants- 4 families

HISTORY

• In the mid 1950s-water can pass through some pores

• Till early 80s-there are some sort of selective filter that prevents ions from passing through the membrane while water molecules can pass

• In the mid-1980s Peter Agre studied various membrane proteins from the red blood cells and also found one of these in the kidney.

• Having determined both its peptide sequence and the corresponding DNA sequence, he realised that this must be the protein that so many had sought before him: the cellular water channel.

• In 1992 Peter Agre at John Hopkins University reported his unintentional discovery of aquaporin, he earned a Nobel Prize for his discovery in 2003 .

HISTORY..

Crystallographic structure of the aquaporin 1 (AQP1) channel (PDB 1J4N)

STRUCTURE

•  Aquaporin appear to assemble in membranes as homotetramers in which each monomer, consisting of six membrane-spanning α-helical domains with cytoplasmically oriented amino and carboxy termini.

•  two well-known channel constriction sites in the peptide are NPA motif and a second and usually narrower constriction known as 'selectivity filter' or ar/R selectivity filter.

NPA Motif

STRUCTURE..

www.sigma-aldrich.com

STRUCTURE..

ar/R selectivity filter

Importance of Aquaporins• Aquaporin are known to play a big role in

various aspects of normal body function.• Many mammalian AQPs, including AQP1,

AQP2, AQP4, AQP5 and AQP8, function primarily as bidirectional water-selective transporters.

• It is seen that most, if not all, significant biological functions of the mammalian AQPs, can be attributed to AQP facilitated water and/or glycerol transport.

• In oocytes it transport glycerol and to some extent urea, along with water.

Diseases

• Several diseases such as congenital cataracts and nephrogenic diabetes insipidus are relate to mutations in aquaporins, also fluid transport, brain swelling, strokes, meningities, multiple sclerosis.

• A small number of people are found with a deficiency of aquaporins and they generally seem healthy, but they have a defect in the ability to concentrate solutes in urine and to conserve water when deprived of drinking water

THANK YOU !!!

References

• Aquaporin water channels: molecular mechanisms for human diseases1-by Peter Agre, David Kozono

• Aquaporins at a glance byAlan S. Verkman• http

://www.ks.uiuc.edu/Research/aquaporins/• http://www.aquaporins.org/disease.htm• http://www.hopkinsmedicine.org/press/2003

/october/031008a.htm

• http://en.wikipedia.org/wiki/Aquaporin