Structural characterisation of a MAPR-related archaeal cytochrome b_5M protein

Area of Science:

• Biochemistry
• Structural Biology
• Evolutionary Biology

Background:

• The membrane-associated progesterone receptor (MAPR) protein family, including PGRMC1, PGRMC2, NEUFC, and NENF, has prokaryotic origins.
• MAPR proteins are derived from a novel class of prokaryotic cytochrome b5 (cytb5) domain proteins, termed cytb5M (MAPR-like).
• Classical cytb5 proteins differ from cytb5M and MAPR proteins in sequence elements and heme-binding orientation.

Purpose of the Study:

• To present the crystal structure of an archaeal cytb5M domain.
• To compare the heme-binding orientation of archaeal cytb5M with previously determined cytb5M structures.
• To provide evidence for the evolutionary inheritance of MAPR-like heme orientation from prokaryotic ancestors.

Main Methods:

• X-ray crystallography was used to determine the structure of the archaeal cytb5M domain from Methanococcoides burtonii (PDB: 6VZ6).
• Structural analysis focused on the heme-binding site and its orientation within the protein.
• Comparative analysis was performed with the archetypal cytb5M structure (PDB: 6NZX).

Main Results:

• The crystal structure of the archaeal cytb5M domain was successfully determined.
• The archaeal cytb5M exhibits a heme-binding orientation similar to the previously reported cytb5M structure (6NZX).
• This conserved heme orientation is approximately 90° rotated relative to classical cytb5 proteins.

Conclusions:

• The structural similarity supports the hypothesis that the MAPR-like heme orientation originated from a prokaryotic ancestor.
• The findings reinforce the evolutionary link between prokaryotic cytb5M proteins and eukaryotic MAPR proteins.
• This study provides crucial structural insights into the early evolution of this protein family.