Dr. Hisham Mazal

  • Postdoctoral Fellow
  • Room: A.3.246
  • Telephone: +49 9131 7133343
  • E-mail

My main research goal is to develop state-of-the-art single-particle cryogenic super-resolution fluorescence microscopy to uncover the intricate structures of soluble and membrane proteins in their native environments.

Additionally, our aim is to establish a streamlined workflow for freeze-preserved specimens enabling correlative structural biology studies using the two powerful microscopy approaches of cryogenic super-resolution light and electron microscopy.

2024

Higher order transient membrane protein structures

Yuxi Zhang, Hisham Mazal, Venkata Shiva Mandala, Gonzalo Perez-Mitta, Vahid Sandoghdar, Christoph A. Haselwandter, Roderick McKinnon

Proceedings of the National Academy of Sciences of the United States of America 122 e2421275121 (2024) | Journal | PDF

This study shows that five membrane proteins—three GPCRs, an ion channel, and an enzyme—form self-clusters under natural expression levels in a cardiac-derived cell line. The cluster size distributions imply that these proteins self-oligomerize reversibly through weak interactions. When the concentration of the proteins is increased through heterologous expression, the cluster size distributions approach a critical distribution at which point a phase transition occurs, yielding larger bulk phase clusters. A thermodynamic model like that explaining micellization of amphiphiles and lipid membrane formation accounts for this behavior. We propose that many membrane proteins exist as oligomers that form through weak interactions, which we call higher-order transient structures (HOTS). The key characteristics of HOTS are transience, molecular specificity, and a monotonically decreasing size distribution that may become critical at high concentrations. Because molecular specificity invokes self-recognition through protein sequence and structure, we propose that HOTS are genetically encoded supramolecular units.

Hisham Mazal studied Biotechnology Engineering (BSc) at ORT Braude Academic College of Engineering (Israel) from 2010 to 2013 and Chemical and Biological Physics (MSc) at Weizmann Institute of Science (Israel) from 2013 to 2015 as an undergraduate student. From 2016 to 2020 he continued at Weizmann Institute for his PhD thesis on “Single-molecule protein dynamics: From ligand binding effects on folding to function-related motions” and as a postdoc. In June 2020 Hisham Mazal joined the group of Prof. Vahid Sandoghdar at MPL as a postdoc.

MPL Research Centers and Schools