Conformational Changes

Conformational Changes in Proteins - III

Lactoferrin is an iron binding protein found in secretions such as tears and milk.

It is folded into two large lobes, each of which consists of two domains.

The iron binding sites are between the domains.

When the protein releases its iron, the N-terminal lobe opens up, but strangely, the C-terminal one remains largely closed.

Lactoferrin, with Fe Bound (1lfg)	Lactoferrin without Fe (1lfh)

The motion of the N-terminal lobe is largely a hinge motion;

the domains retain most of their structure, and simply open like a lobster claw
The residues at the hinge are Arg89, Thr90, His91, Tyr92.

Lactoferrin, with Fe Bound (1lfg) Lactoferrin without Fe (1lfh)
The Tyr group seems to have rotated away from the iron, and there has been a substantial rotation, almost 180^o, of the Thr.
Overall, a fit of the protein with and without iron gives an rms deveiation of about 1.01 A:

Superposition of 1lfg and 1lfh
The two domains that move superpose on themselves with and without iron with rms deviations of about 0.7 A,
Taken together (less the other lobe), the deviation is more than 6 A.

Here is a little movie, showing lactoferrin's conformational change:

Lactoferrin in Motion

More such movies are available from the Gerstein group at Yale, which maintains a database of protein motions.

An obvious question arises: what initiates the release of the iron? We could argue that closing on the iron is driven by electrostatics, but what drives releasing it? And why does only one lobe undergo this dramatic change?

If you'd like to search for answers to these questions, feel free to substitute what you find for one of the questions on the next problem set.

This page last modified 11:00 AM on Friday March 2nd, 2012.
Webmaster, Department of Chemistry, University of Maine, Orono, ME 04469