Polar residues in the membrane core are conserved and directly involved in function

• Here, we have analyzed strongly polar residues within the membrane core of alpha-helicalmembrane proteins. Although underrepresented, they constitute as much as 9% of all coreresidues and they are found to be more conserved than other core residues. The reason for theconservation is twofold. First, the residues are mainly buried within the proteins and secon-darily they are found to often be directly involved in the function of the protein. Even if mostpolar sidechains are buried, the actual polar groups often border water filled cavities. In addi-tion, polar residues are often directly involved in binding of small compounds in channels andtransporters or long-term interactions with prosthetic groups. The interactions with prostheticgroups in photosynthetic proteins and oxidoreductase proteins are dominated by histidines andflexibility is provided mainly by prolines. It was also predicted that in human membrane pro-teins the polar core residues are overrepresented among active transporter proteins as well asamong GPCRs, while underrepresented in families with few transmembrane regions, such asnon-GPCR receptors. In GPCRs asparagin, histidine and proline residues are overrepresentedwhile in the active transporters prolines and glutamates are most frequent.

Keyword

Membrane proteins

polar residues

conservation

accessibility

functional residues

Publication and Content Type

vet (subject category)

ovr (subject category)