[Seminar] Exploring Membrane Protein Landscape: Experience from the New York Consortium on Membrane Protein Structure (NYCOMPS)

Seminar

Title: Exploring Membrane Protein Landscape: Experience from the
New York Consortium on Membrane Protein Structure (NYCOMPS)

Speaker: Filippo Mancia

Affiliation: Department of Physiology and Cellular Biophysics, Columbia University, New York, USA

Host: Margarida Archer, Membrane Protein Crystallography Lab

Abstract:

Membrane proteins play critical roles in cellular processes and in human health and disease. Despite their importance, knowledge of their atomic structure lags far behind that of soluble proteins due to numerous difficulties posed in their expression, purification and crystallization— all pre-requisites for structure determination by x-ray crystallography, the most successful technique available to obtain an atomic resolution model. Advances in recent years have made use of naturally occurring or synthetically engineered variations in the protein’s sequence to maximize crystallization probabilities. High-throughput platforms have been instrumental to improved success. They allow selection of proteins that have an increased probability of crystallization at an early stage of the process.
We have established the New York Consortium on Membrane Protein Structure (NYCOMPS). The overall objective of NYCOMPS is to accelerate the acquisition of structural information about membrane proteins by applying a structural genomics approach informed by the collective experience of a team of expert investigators to work together toward this objective. Our pipeline for structure determination selects targets through a bioinformatics analysis of all known sequences, moves on to recombinant cloning, protein expression and protein purification at moderately high throughput, and then completes structures by x-ray crystallography. Targets are
identified through nominations from the biological community and from NYCOMPS biological themes. Our Protein Production Facility at the New York Structural Biology Center (NYSBC) handles targets through purification at a mid-scale level, and successful candidates are distributed to participant laboratories for scale-up and crystallization. Functional analysis of structures is performed both by computations and through routine experimental biochemistry.