BioPHYSICAL chemistry

The availability of several different structures of porins has provided a

molecular basis for the conductance of molecules in transporters. Porins

are molecules that allow the passage of different molecules through the

membrane. The porins from the outer membrane, such as FhuA, which

is an iron transporter, are β-barrels with a large central channel and a

domain that can cover the channel. The aquaporins are a family of 30-kDa

proteins that are found throughout all kingdoms and in all species and

regulate the movement of water and aliphatic alcohols across the cell

membrane. When open, the rate of conductance is extremely rapid at

about 10^9 s−^1 , which is close to the diffusion limit of water molecules, with-

out sacrificing selectivity, as the transport of other solutes is negligible.

The structure shows eight transmembrane helices folded around a central

channel, which is shaped like an hourglass and has a width that varies

from 3.5 to 15 Å (Figure 18.5). In the structure of the glycerol transporter,

three bound glycerol molecules were found occupying the central channel.

Conduction through the channel is regulated by a number of interactions.

The initial wide opening allows the water molecules or substrate mole-

cule to maintain hydrogen bonding with the surrounding water. The

channel has a narrow region to filter molecules based on their size. Proton

conduction in the form of H 3 O+is prevented by electrostatic interactions

with amino acid residues that line the channel and the dipoles of short

αhelices. Computer simulations of the passage of water suggest that the

water molecules rotate and become aligned through dipole interactions

as they travel though the channel.

396 PART 3 UNDERSTANDING BIOLOGICAL SYSTEMS USING PHYSICAL CHEMISTRY

K300

IX D133

(c)

XIp

Downregulated conformation (pH  6.5) Active conformations (pH  6.5)

IVp

V

D164

D163

T132

1Na/Li 2H

1Na/Li 2H

IVc XIc

K300

IX D133

(b)

V

T132

XIp IVp

K300

IX

(a)

Cytoplasm

Periplasm

D163

XIp IVp

V

D133

D164

T132

IVc XIc IVc XIc

XIp IVp

D164D163

Figure 18.4A possible mechanism for the regulation of translocation of molecules based upon the
structure of the Na+/H+antiporter. (a) Under acidic conditions, transport is blocked. (b) Activation
by alkaline pH. (c) Na+(Li+) results in opening on the periplasmic side. Modified from Hunte et al.
(2005).