You are interested in the function of a protein, Mtm1, that has a PH domain, an

Question

You are interested in the function of a protein, Mtm1, that has a PH domain, an SH3 domain, and a PTB domain. Mtm1 functions downstream of the insulin receptor and binds to this receptor in an insulin-dependent fashion via its PTB domain. You create mutant forms of Mtm1 that delete the various protein domains. You find that these mutations do not seem to affect the protein level or folding of Mtm1. You examine the localization of Mtm1 and your results are summarized in Table 2.

In Table 2, the D symbol indicates that the following protein domain is deleted. For example, mtm1DPH indicates an Mtm1 protein that lacks the PH domain; mtm1DPHDSH3 indicates an mtm1 protein that lacks both the PH domain and the SH3 domain. Given what you know about these three protein domains and the data above, explain the role of the PH, PTB, and SH3 domains in localizing the Mtm1 protein.

localization no insulirn with insulin added plasma membranecytoplasmic plasma membrane Mtm1 mtm1DPH mtm 1DSH3 mtm1DPTB mtm 1DPHDSH3 mtm1DPHDPTB mtm1DPTBDSH3 Table 2

Explanation / Answer

Without insulin, the Mtm protein will not be able to bind to the plasma membrae even with the aid of any of the domains.

After adding insulin,

PH domain deletion favours localisation of Mtm in cytoplasm

SH3 domain deletion favours localisation of Mtm in plasma membrane

PTB domain favours localisation of Mtm in cytoplasm, much more than PH domain deletion.

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